Journal articles on the topic 'Adrenal medulla – Metabolism'
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1
Macdonald, I. A., T. Bennett, and I. W. Fellows. "Catecholamines and the control of metabolism in man." Clinical Science 68, no. 6 (June 1, 1985): 613–19. http://dx.doi.org/10.1042/cs0680613.
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Introduction: The physiological effects of catecholamines can result from a combination of increased activity of the sympathetic nervous system and secretion from the adrenal medulla. However, studies in the rat have revealed circumstances in which adrenal medullary secretion can occur at a time when the activity of the sympathetic nervous system is suppressed [1]; furthermore, in the lamb there may be variations in the relative amounts of noradrenaline and adrenaline secreted from the adrenal medulla [2]. It is not known whether such phenomena occur in man.
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Coulter, C. L., H. M. Mulvogue, I. R. Young, C. A. Browne, and I. C. McMillen. "Effect of fetal hypophysectomy on the localization of the catecholamine biosynthetic enzymes and enkephalins in the adrenal medulla of the fetal sheep." Journal of Endocrinology 121, no. 3 (June 1989): 425—NP. http://dx.doi.org/10.1677/joe.0.1210425.
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ABSTRACT We have investigated the effect of fetal hypophysectomy on the localization of dopamine B-hydroxylase (DBH), phenylethanolamine N-methyltransferase (PNMT) and enkephalin-containing peptides in the fetal sheep adrenal, using immunocytochemical techniques. Staining with anti-DBH was observed throughout the adrenal medulla in the intact (140–146 days of gestation) and hypophysectomized fetal sheep (147–164 days of gestation) and the newborn lamb (10–12 days after birth). In the adrenal medulla of the lategestation intact fetal sheep and newborn lamb, positive staining with anti-PNMT was observed in the peripheral rim of medullary cells adjacent to the adrenal cortex. After hypophysectomy, there was intense positive staining with anti-PNMT in the peripheral adrenal medullary cells and a small and variable proportion of central adrenal medullary cells were stained with anti-PNMT. In the adrenal gland of the intact fetal sheep and the newborn lamb, there was intense staining with anti-enkephalin in the peripheral rim of adrenal medullary cells. Staining with antienkephalin was less intense in the central medullary cells of the adrenal gland of the intact fetal sheep and the 10- to 12-day-old newborn lamb, and many unstained central medullary cells were present. After hypophysectomy, intense positive staining with antienkephalin was observed throughout the entire fetal adrenal medulla. Therefore, the fetal pituitary, either directly or indirectly through the adrenal cortex, plays a role in regulating the pattern of localization of both PNMT and enkephalin in the fetal sheep adrenal. Journal of Endocrinology (1989) 121, 425–430
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Liu, J., AI Kahri, P. Heikkila, and R. Voutilainen. "Adrenomedullin gene expression and its different regulation in human adrenocortical and medullary tumors." Journal of Endocrinology 155, no. 3 (December 1, 1997): 483–90. http://dx.doi.org/10.1677/joe.0.1550483.
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Adrenomedullin (ADM) is a polypeptide originally discovered in a human pheochromocytoma and is also present in normal adrenal medulla. It has been proposed that ADM could be involved in the regulation of adrenal steroidogenesis via paracrine mechanisms. Our aim was to find out if ADM gene is expressed in adrenocortical tumors and how ADM gene expression is regulated in adrenal cells. ADM mRNA was detectable by Northern blotting in most normal and hyperplastic adrenals, adenomas and carcinomas. The average concentration of ADM mRNA in the hormonally active adrenocortical adenomas was about 80% and 7% of that in normal adrenal glands and separated adrenal medulla respectively. In adrenocortical carcinomas, the ADM mRNA concentration was very variable, but on average it was about six times greater than that in normal adrenal glands. In pheochromocytomas, ADM mRNA expression was about ten times greater than that in normal adrenals and three times greater than in separated adrenal medulla. In primary cultures of normal adrenal cells, a protein kinase C inhibitor, staurosporine, reduced ADM mRNA accumulation in a dose- and time-dependent fashion (P < 0.01), whereas it simultaneously increased the expression of human cholesterol side-chain cleavage enzyme (P450 scc) gene (a key gene in steroidogenesis). In cultured Cushing's adenoma cells, adrenocorticotropin, dibutyryl cAMP ((Bu)2cAMP) and staurosporine inhibited the accumulation of ADM mRNA by 40, 50 and 70% respectively (P < 0.05), whereas the protein kinase C activator, 12-O-tetradecanoyl phorbol 13-acetate (TPA), increased it by 50% (P < 0.05). In primary cultures of pheochromocytoma cells, treatment with (Bu)2cAMP for 1 and 3 days increased ADM mRNA accumulation two- to threefold (P < 0.05). Our results show that ADM mRNA is present not only in adrenal medulla and pheochromocytomas, but also in adrenocortical neoplasms. Both protein kinase A- and C-dependent mechanisms regulate ADM mRNA expression in adrenocortical and pheochromocytoma cells supporting the suggested role for ADM as an autocrine or paracrine (or both) regulator of adrenal function.
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Chabot, J. G., P. Walker, and G. Pelletier. "Distribution of epidermal growth factor binding sites in the adult rat adrenal gland by light microscope autoradiography." Acta Endocrinologica 113, no. 3 (November 1986): 391–95. http://dx.doi.org/10.1530/acta.0.1130391.
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Abstract. The distribution of epidermal growth factor (EGF) receptors was studied in the adrenal gland using light microscope autoradiography which was carried out 2 min after intravenous (iv) injection of [125I]EGF into adult rat. At the light microscope level, the labelling was found over the cells of the capsule and adrenal medullary chromaffin cells. No specific labelling of the steroid-secreting cells was observed. Control experiments indicated that the autoradiography reaction was due to specific interaction of [125I]EGF with its receptor. These results clearly indicate that EGF receptors are present in the majority of the adrenal medulla cells. They suggest that EGF may exert a physiological role in the regulation of rat adrenal medulla.
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Liu, J., R. Voutilainen, A. I. Kahri, and P. Heikkilä. "Expression patterns of the c-myc gene in adrenocortical tumors and pheochromocytomas." Journal of Endocrinology 152, no. 2 (February 1997): 175–81. http://dx.doi.org/10.1677/joe.0.1520175.
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Abstract Abundant c-myc gene expression in neoplasms has been often linked to poor prognosis. As c-myc mRNA is expressed and hormonally regulated in human adrenals, we examined the c-myc gene expression in adrenal tumors by RNA analysis and immunohistochemistry to find out the possible role of c-myc in adrenal neoplasms. The abundant expression of the c-myc gene in normal adrenals was localized to the zona fasciculata and zona reticularis, with much lower expression in the zona glomerulosa and adrenal medulla. In hormonally active adrenocortical carcinomas (n=6) and in virilizing adenomas (n=4), c-myc mRNA levels were approximately 10% of those in normal adrenals (n=11). In contrast, adrenal adenomas from patients with Cushing's (n=4) and Conn's (n=9) syndrome, non-functional adenomas (n=2), adrenocortical hyperplasias (bilateral, n=5; nodular, n=4), and non-functional adrenocortical carcinomas (n=3) expressed c-myc mRNA to the same extent as normal adrenals. The c-myc mRNA abundance in benign adrenal pheochromocytomas (n=19) was similar to that in normal adrenal medulla. However, in malignant adrenal pheochromocytomas (n=6), the average c-myc mRNA levels were approximately threefold that in benign adrenal pheochromocytomas. There was a good correlation between c-myc mRNA expression and immunohistochemical reactivity in both normal and pathological adrenal tissues. Southern blot analysis revealed no amplification or rearrangement of the c-myc gene in any of the adrenal tumors. In conclusion, c-myc expression localized to zona fasciculata and reticularis in normal adrenals. Virilizing adenomas and hormonally active adrenocortical carcinomas expressed c-myc mRNA clearly less than the other adrenal neoplasms and normal adrenal tissue. On the other hand, malignant pheochromocytomas contained more c-myc mRNA than benign ones. Further studies are required to clarify the mechanisms and significance for the distinct expression pattern of the c-myc gene in different adrenal neoplasms. Journal of Endocrinology (1997) 152, 175–181
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Fukuda, Tsuyoshi, Kazuhiro Takahashi, Takashi Suzuki, Masayuki Saruta, Mika Watanabe, Taisuke Nakata, and Hironobu Sasano. "Urocortin 1, Urocortin 3/Stresscopin, and Corticotropin-Releasing Factor Receptors in Human Adrenal and Its Disorders." Journal of Clinical Endocrinology & Metabolism 90, no. 8 (August 1, 2005): 4671–78. http://dx.doi.org/10.1210/jc.2005-0090.
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Abstract Context: Urocortin 1 (Ucn1) and urocortin 3 (Ucn3)/stresscopin are new members of the corticotropin-releasing factor (CRF) neuropeptide family. Ucn1 binds to both CRF type 1 (CRF1) and type 2 receptors (CRF2), whereas Ucn3 is a specific agonist for CRF2. Recently, direct involvement of the locally synthesized CRF family in adrenocortical function has been proposed. Objective, Design, and Setting: We examined in situ expression of Ucn and CRF receptors in nonpathological human adrenal gland and its disorders using immunohistochemistry and mRNA in situ hybridization. Results: Ucn immunoreactivity was localized in the cortex and medulla of nonpathological adrenal glands. Ucn1 immunoreactivity was marked in the medulla, whereas Ucn3 was immunostained mostly in the cortex. Both CRF type 1 and CRF2 were expressed in the cortex, particularly in the zonae fasciculata and reticularis but very weakly or undetectably in the medulla. Immunohistochemistry in serial tissue sections with mirror images revealed that both Ucn3 and CRF2 were colocalized in more than 85% of the adrenocortical cells. mRNA in situ hybridization confirmed these findings above. In fetal adrenals, Ucn and CRF receptors were expressed in both fetal and definitive zones of the cortex. Ucn and CRF receptors were all expressed in the tumor cells of pheochromocytomas, adrenocortical adenomas, and carcinomas, but its positivity was less than that in nonpathological adrenal glands, suggesting that Ucn1, Ucn3, and CRF receptors were down-regulated in these adrenal neoplasms. Conclusions: Ucn1, Ucn3, and CRF receptors are all expressed in human adrenal cortex and medulla and may play important roles in physiological adrenal functions.
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McMillen, I. C., H. M. Mulvogue, C. L. Coulter, C. A. Browne, and P. R. C. Howe. "Ontogeny of catecholamine-synthesizing enzymes and enkephalins in the sheep adrenal medulla: an immunocytochemical study." Journal of Endocrinology 118, no. 2 (August 1988): 221—NP. http://dx.doi.org/10.1677/joe.0.1180221.
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ABSTRACT An immunocytochemical staining technique was used to investigate the development of the sheep adrenal medullary cells containing enkephalins and the catecholamine synthetic enzymes dopamine β-hydroxylase (DBH) and phenylethanolamine N-methyl transferase (PNMT). No staining was observed in the adrenocortical cells with any of the antisera used in this study. Positive staining with anti-DBH was observed throughout the medulla in both adult and fetal adrenal glands from 80 days of gestation. Positive staining with anti-PNMT was observed in all glands from as early as 80 days of gestation, and staining with this antiserum was mainly confined to the peripheral medullary cells, which were adjacent to, and interdigitated between, the cells of the adrenal cortex. In the fetus between 80 and 120 days of gestation, staining for the enkephalins was observed in both the peripheral columnar and the central polygonal adrenal medullary cells. After 125 days of gestation and in the adult ewe, the peripheral columnar cells were uniformly stained with anti-enkephalin whereas many unstained cells were present in the central medullary region. Therefore, enkephalin-containing peptides are present in the catecholamine cells of the fetal and adult sheep adrenal and there appears to be a changing pattern in the distribution of the enkephalins in the fetal adrenal in late gestation. J. Endocr. (1988) 118, 221–226
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Nussey, S. S., R. A. Prysor-Jones, A. Taylor, V. T. Y. Ang, and J. S. Jenkins. "Arginine vasopressin and oxytocin in the bovine adrenal gland." Journal of Endocrinology 115, no. 1 (October 1987): 141–49. http://dx.doi.org/10.1677/joe.0.1150141.
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ABSTRACT The concentrations of immunoreactive oxytocin and arginine vasopressin (AVP) and their respective neurophysins (NpI and NpII) were compared in bovine adrenal cortex and medulla. While the concentration of AVP was similar in both tissues there was more NpII in the medulla. The medulla also contained much more oxytocin and NpI than the cortex. The extracted AVP and oxytocin had identical retention times to those of the synthetic peptides on high-performance liquid chromatography (HPLC) and were biologically active in assays for antidiuretic and milk-ejection activity (with potencies of 310 units/mg and 340 units/mg respectively). Adrenal NpI and NpII behaved identically to commercially available neurohypophysial proteins on HPLC. Oxytocin, NpI and AVP were assayed in five subcellular fractions of bovine adrenal medulla prepared on discontinuous sucrose gradients. A high proportion of each co-localized with noradrenaline and adrenaline in the chromaffin granule fraction. Binding of [3H]AVP and [3H]oxytocin to crude bovine adrenal medulla membranes was dependent upon both time and temperature. The binding sites were specific and saturable: studies with the V1 AVP antagonist d(CH2)5Tyr(Me)AVP and the V2 agonist 1-deamino-8-d-AVP indicated that the AVP receptor was V1 in specificity. Scatchard plots showed that each ligand interacted with a single high-affinity, low-capacity binding site: oxytocin dissociation constant (Kd) 3·1 ±0·29 nmol/l, maximum binding capacity (Bmax) 89·6 ±18·4 fmol/mg protein (n = 3); AVP Kd 0·73 ±0·02 nmol/l, Bmax 26·5 ±8·3 fmol/mg protein (n = 3). Oxytocin and AVP had no effect on basal catecholamine release from bovine chromaffin cells in primary monolayer culture. However, both peptides inhibited acetylcholine- or nicotine-stimulated noradrenaline and adrenaline release in a dose-related manner. Neither inhibited noradrenaline or adrenaline secretion stimulated by veratridine- or potassium-induced depolarization. We conclude that the bovine adrenal cortex and medulla contain authentic AVP and oxytocin. In the medulla the peptides are packaged in secretory granules. The presence of the related neurophysins and high-affinity receptors in the medulla suggests that the peptides are both synthesized and have their site of action within this tissue. The function of AVP and oxytocin in the medulla may be indicated by the inhibition of acetylcholine-stimulated catecholamine secretion in vitro, although the effect requires high concentrations of either peptide. J. Endocr. (1987) 115, 141–149
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Inoue, Aiko, Sachika Inoue, Rui Sawai, Keita Hamamatsu, Kyoko Okazaki, Hitoshi Nishizawa, Yuto Yamazaki, Hironobu Sasano, Hiroyuki Murabe, and Toshihiko Yokota. "Mixed Corticomedullary Tumors of the Adrenal Gland Harboring Both Medullary and Cortical Properties." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A143. http://dx.doi.org/10.1210/jendso/bvab048.289.
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Abstract Adrenal cortex and medulla are derived from mesoderm and ectoderm, respectively. Mixed corticomedullary tumors (MCMTs), comprising an intimately admixed population of both adrenal cortical cells and pheochromocytes in a single adrenal tumor, are extremely rare and its pathogenesis has remained unknown. Here, we report a case of MCMT whose cells co-expressed cortical and medullary antigens in the same tumor cells.[Case description]A 40-year-old woman was referred to our hospital for investigating Takotsubo cardiomyopathy following resection of uterine fibroids. An abdominal CT scan depicted a 24 mm tumor on her left adrenal gland. Her basal serum ACTH, cortisol levels and urinary cortisol were 13.8 pg/mL, 9.5 μg/dL, and 26.5 μg/day respectively. The cortisol level was normally suppressed by an administration of 1 mg dexamethasone (1.4 μg/dL). Plasma renin activity, aldosterone levels and urinary aldosterone were 15.0 ng/mL/h, 122 pg/mL, and 5.0 μg/day, respectively (with administration history of azosemide). On the other hand, her plasma adrenaline and noradrenaline levels were elevated as high as 177 pg/mL and 536 pg/mL, and urinary metanephrine and normetanephrine were 2.12 mg/day and 1.10 mg/day. A 123I-metaiodobenzylguanidine scan revealed high uptake in the tumor. After adequate adrenergic α-receptor blockage, left adrenalectomy was performed. Her postoperative endocrine and clinical findings were normalized without any further complications.[Pathology] Immunohistochemistry (IHC) revealed the presence of MCMT. Cells morphologically consistent with pheochromocytoma and adrenocortical cells were confirmed by immunostaining of chromogranin A and SF-1, respectively. Chromogranin A-positive medullary-derived and SF-1-positive cortical-derived tumor cells were intermixed in the chimeric fashion. In addition, some tumor cells were positive for both proteins, indicating hybrid nature of the cells. Tumor cells of cortical origin expressed CYP11β1, 3β-HSD, p450c21, and p450c17, but not CYP11β2. Non neoplastic adrenal cortex were atrophic, whereas the glomerulosa was hyperplastic positive for CYP11β2, consistent with diffuse hyperplasia and adrenal medullar unremarkable. [Conclusions:]The adrenal tumor was clinically diagnosed as pheochromocytoma, but the pathological findings did reveal cortisol production in the tumor and aldosterone overproduction in the accompanying cortex. This is the first case of MCMT co-expressing adrenal medullary and cortical antigens in the same tumor cells as hybrid cells.
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Breslow, M. J., J. R. Tobin, T. D. Mandrell, L. C. Racusen, H. Raff, and R. J. Traystman. "Changes in adrenal oxygen consumption during catecholamine secretion in anesthetized dogs." American Journal of Physiology-Heart and Circulatory Physiology 259, no. 3 (September 1, 1990): H681—H688. http://dx.doi.org/10.1152/ajpheart.1990.259.3.h681.
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Prior attempts to study adrenal medullary O2 metabolism during catecholamine secretion have been unsuccessful because venous blood from medulla mixes with venous blood from the much larger cortex. To circumvent this problem, eight adult mongrel dogs were pretreated for 5-6 wk with the adrenocorticolytic agent 1,1-dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)ethane (o,p'-DDD). Prednisolone (5 mg/day) and fludrocortisone (0.1 mg.10 kg-1.day-1) were administered orally to prevent adrenocortical insufficiency. Animals were then anesthetized with pentobarbital sodium and subjected to splanchnic nerve stimulation (NS) at 20 and 4 Hz to elicit catecholamine secretion. NS at 20 Hz increased epinephrine secretion from 1.6 +/- 0.7 to 1,780 +/- 762 ng.min-1.g medulla-1 but had no effect on medullary O2 consumption. Medullary blood flow (MQ) increased from 216 +/- 63 to 1,522 +/- 182 ml.min-1.100 g-1, and O2 extraction decreased from 2.7 +/- 0.7 to 0.8 +/- 0.2%. NS at 4 Hz increased epinephrine secretion from 3.1 +/- 1.4 to 76 +/- 17 ng.min-1.g medulla-1 and MQ from 226 +/- 66 to 649 +/- 122 ml.min-1.100 g-1 but had no effect on adrenal O2 consumption or extraction. Cortical blood flow was 342 +/- 98 ml.min-1.100 g-1 at baseline and was unaffected by NS. Gross weight of cortex was reduced by 80% in o,p'-DDD-treated animals, and histological examination of glands from three animals showed only rare islands of glomerulosa cells remaining. These data suggest that increases in MQ during NS do not occur in response to changes in O2 consumption.
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Baquedano, María Sonia, Nora Saraco, Esperanza Berensztein, Carolina Pepe, Michele Bianchini, Estrella Levy, Javier Goñi, Marco A. Rivarola, and Alicia Belgorosky. "Identification and Developmental Changes of Aromatase and Estrogen Receptor Expression in Prepubertal and Pubertal Human Adrenal Tissues." Journal of Clinical Endocrinology & Metabolism 92, no. 6 (June 1, 2007): 2215–22. http://dx.doi.org/10.1210/jc.2006-2329.
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Abstract Context: The mechanisms of postnatal adrenal zonation remain unclear. Objective: To provide a clue for a possible role of estrogens in adrenarche, we studied the expression of estrogen receptor (ER)α, ERβ, G protein-coupled receptor (GPR)30, and cP450aromatase (cP450arom) in human adrenal tissue. Design: Human adrenal tissue was collected from three postnatal age groups (Grs): Gr 1, younger than 3 months (n = 12), fetal zone involution; Gr 2, 3 months to 6 yr (n = 17), pre-adrenarche; and Gr 3, older than 6–20 yr (n = 12), post-adrenarche period. Results: ERβ mRNA in Grs 1 and 3 was higher than in Gr 2 (P < 0.05). By immunohistochemistry and laser capture microdissection followed by RT-PCR, ERβ was expressed in zona reticularis and fetal zone, GPR30 in zona glomerulosa (ZG) and adrenal medulla, while ERα mRNA and protein were undetectable. cP450arom mRNA in Gr 3 was higher than in Grs 1 and 2 (P < 0.05), and localized to ZG and adrenal medulla by laser capture microdissection. cP450arom Immunoreactivity was observed in adrenal medulla in the three Grs and in subcapsular ZG of Gr 3. Double-immunofluorescence studies revealed that cP450arom and chromogranin A only colocalize in adrenal medulla of subjects younger than 18 months. In these samples, exon 1.b-derived transcript was 3.5-fold higher, while exon 1.a-, 1.c-, and 1.d-derived transcripts were 3.3-, 1.9-, and 1.7-fold lower, respectively, than in subjects older than 6 yr. Conclusions: Our results suggest that estrogens produced locally in adrenal medulla would play a role in zona reticularis functional differentiation through ERβ. The cP450arom and GPR30 expression in subcapsular ZG, colocalizing with a high-cell proliferation index, previously reported, suggests a local GPR30-dependent estrogen action in proliferation and migration of progenitor adrenal cells.
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Watanabe, T., N. Shimamoto, A. Takahashi, and M. Fujino. "PACAP stimulates catecholamine release from adrenal medulla: a novel noncholinergic secretagogue." American Journal of Physiology-Endocrinology and Metabolism 269, no. 5 (November 1, 1995): E903—E909. http://dx.doi.org/10.1152/ajpendo.1995.269.5.e903.
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The secretory response of the adrenal medulla to pituitary adenylate cyclase-activating polypeptide (PACAP), a novel polypeptide with 68% structural homology to vasoactive intestinal polypeptide (VIP), was investigated in anesthetized rats by in vivo microdialysis. The injection of PACAP (1.5 nmol) caused a greater amount of increase in catecholamine concentration than carbachol (30 nmol) or VIP (30 nmol) in the dialysate for a period of 60 min. The ratios of norepinephrine to epinephrine in the dialysate after stimulation with these compounds showed no change from resting conditions. The simultaneous application of both nicotinic and muscarinic antagonists (10 mM mecamylamine and 1 mM atropine) eliminated the increase in catecholamine secretion induced by carbachol. In contrast, PACAP-induced catecholamine secretion was not inhibited by these cholinergic antagonists. These data led to the following conclusions: 1) PACAP was more potent than either carbachol or VIP in enhancing the secretion of catecholamine from the adrenal medulla, and 2) PACAP-induced catecholamine secretion was due to the direct action of PACAP on the adrenal medulla rather than an indirect action mediated by acetylcholine release. These results strongly suggest that PACAP is a noncholinergic secretagogue of the adrenal medulla in rats.
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O'Connor, Daniel T. "The adrenal medulla, vol. 4." Psychoneuroendocrinology 12, no. 5 (January 1987): 407. http://dx.doi.org/10.1016/0306-4530(87)90071-0.
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Trevenzoli, I. H., C. R. Pinheiro, E. P. S. Conceição, E. Oliveira, M. C. F. Passos, P. C. Lisboa, and E. G. Moura. "Programming of rat adrenal medulla by neonatal hyperleptinemia: adrenal morphology, catecholamine secretion, and leptin signaling pathway." American Journal of Physiology-Endocrinology and Metabolism 298, no. 5 (May 2010): E941—E949. http://dx.doi.org/10.1152/ajpendo.00734.2009.
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Leptin serum concentration in early life is an important factor for adequate future development of the offspring. Previously, we demonstrated that hyperleptinemia on lactation programmed for hyperleptinemia, central leptin resistance with lower expression of the long form of leptin receptor at hypothalamus, and higher medullary catecholamine levels with cardiovascular consequences at adulthood. The central objective of this study was to determine the direct effect of leptin on adrenal medullary function of adult rats that were leptin treated during lactation. Adrenal morphology was also accessed. Recombinant murine leptin was injected in the pups during the first 10 days of life (group L, leptin-programmed) or at adulthood during 6 days (group LC). The controls of both experiments received saline (groups C and CC). Both treatments resulted in hyperleptinemia at 150 days old (+78% and 2-fold increase, respectively; P < 0.05). Programmed animals showed hypertrophy of adrenal and higher adrenal catecholamine content at 150 days old (3-fold increase, P < 0.05), and no changes were observed in the LC group. However, LC rats had lower adrenal content of tyrosine hydroxylase (−17%, P < 0.05). Leptin-programmed rats had a lower response to leptin in vitro stimulation (−22%, P < 0.05) and lower expression of key proteins of the leptin signaling pathway, leptin receptor and janus tyrosine kinase 2 in the medullas (−61% and −29%, respectively, P < 0.05). However, they presented higher expression of phosphorylated signal transducer and activator of transcription 3 (+2-fold, P < 0.05). Leptin treatment at adulthood did not affect these parameters. The higher catecholamine synthesis and secretion in the leptin-programmed rats observed in our previous study does not seem to be a consequence of the direct effect of leptin on the medullas. We suggest that the hyperleptinemia of the programmed animals increases adrenal medullary function through sympathetic nervous system activation. In conclusion, high leptin levels on lactation program the activity of the sympathoadrenal system at adulthood that may contribute to the development of adult chronic diseases such as hypertension.
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Ojuka, E. O., J. D. Bell, G. W. Fellingham, and R. K. Conlee. "Cocaine and exercise: alteration in carbohydrate metabolism in adrenodemedullated rats." Journal of Applied Physiology 80, no. 1 (January 1, 1996): 124–32. http://dx.doi.org/10.1152/jappl.1996.80.1.124.
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The combined treatment of cocaine-exercise (CE) causes an exaggerated catecholamine response, a rapid depletion of muscle glycogen, and accumulation of lactic acid. To assess the contribution of the adrenal medulla in the catecholamine response and to determine the role of epinephrine (Epi) on carbohydrate metabolism, cocaine (20 mg/kg ip) or saline was injected into sham-operated (Sham) or adrenodemedullated (AdM) rats, which then ran for 5 min at 56 m/min, 0% grade. In Sham rats, CE caused plasma Epi values (means +/- SE) to rise to 27.7 +/- 6.9 nM compared with 13.3 +/- 1.5 nM in saline-exercise (SE) and 0.8 +/- 0.2 nM in both AdM-CE and AdM-SE animals (P < 0.05). With minimal Epi in AdM, CE still caused glycogen to fall to lower levels (25.4 +/- 3.0 mumol/g vs. 40.5 +/- 2.4 mumol/g) and lactate to rise to higher levels (17 +/- 3 vs. 9 +/- 1 mumol/kg) in white vastus muscle than in SE group (P < 0.05). CE had no significant effect on soleus and red vastus glycogenolysis but it did cause lactate accumulation in red vastus. As a result, plasma lactate levels were also higher after CE compared with SE in AdM (17.9 +/- 2.0 vs. 8.5 +/- 0.5 mM, P < 0.05). We conclude that during CE 1) Epi is not essential to the alteration in carbohydrate metabolism; 2) the latter may be related to the other catecholamines; 3) the adrenal medulla is the only source of Epi; and 4) the adrenal medulla is not the source of the increased levels of norepinephrine or dopamine.
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Mannelli, M. "Adrenal medulla secretion in Cushing's syndrome." Journal of Clinical Endocrinology & Metabolism 78, no. 6 (June 1, 1994): 1331–35. http://dx.doi.org/10.1210/jc.78.6.1331.
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Keating, Damien J., and Chen Chen. "Activin A stimulates catecholamine secretion from rat adrenal chromaffin cells: a new physiological mechanism." Journal of Endocrinology 186, no. 2 (August 2005): R1—R5. http://dx.doi.org/10.1677/joe.1.06301.
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Activin A is a member of the transforming growth factor-β family and has known roles in the adrenal cortex, from which activin A is secreted. We aimed to find whether activin A induces secretion of catecholamines from chromaffin cells of the adrenal medulla, which neighbours the adrenal cortex in vivo. Using carbon fibre amperometry, we were able to measure catecholamine secretion in real-time from single chromaffin cells dissociated from the rat adrenal medulla. Activin A stimulated catecholamine secretion in a rapid and dose-dependent manner from chromaffin cells. This effect was fully reversible upon washout of activin A. The minimum dose at which activin A had a maximal effect was 2 nM, with an EC50 of 1.1 nM. The degree of secretion induced by activin A (2 nM) was smaller than that due to membrane depolarization caused by an increase in the external K+ concentration from 5 to 70 mM. No response to activin A was seen when Ca2+ channels were blocked by Cd2+ (200 μM). We conclude from these findings that activin A is capable of stimulating a robust level of catecholamine secretion from adrenal chromaffin cells in a concentration-dependent manner. This occurs via the opening of voltage-gated Ca2+ channels, causing Ca2+ entry, thereby triggering exocytosis. These findings illustrate a new physiological role of activin A and a new mechanism in the control of catecholamine secretion from the adrenal medulla.
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Wilburn, Linda A., and Robert B. Jaffe. "Quantitative assessment of the ontogeny of met-enkephalin, norepinephrine and epinephrine in the human fetal adrenal medulla." Acta Endocrinologica 118, no. 3 (July 1988): 453–59. http://dx.doi.org/10.1530/acta.0.1180453.
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Abstract. The catecholamine producing cells of the adrenal medulla of fetal as well as adult mammals contain enkephalins. We have quantified met-enkephalin and the catecholamines, norepinephrine and epinephrine in human fetal adrenal glands during the late first trimester and throughout the second trimester of intrauterine life. Met-enkephalin (ME) was detectable in human fetal adrenals of 11 to 25 weeks' gestation by RIA. ME concentrations were low through 14 weeks (mean 279 ± 199 pg/gland), higher but extremely variable from 15 to 20 weeks (mean 1100 ± 1000 pg/gland), and then lower with somewhat less variation through 25 weeks (mean 865 ± 625 pg/gland). In contrast, catecholamine concentrations were below 1100 ng/gland through 16 weeks, then increased markedly by 21 weeks. Approximately equal concentrations of norepinephrine and epinephrine were measured throughout the gestational age period studied. Our data demonstrate that enkephalin is present in the human fetal adrenal at least by 11 weeks' gestation and suggest that the fetal adrenal may be capable of secreting enkephalins as well as catecholamines. The functional significance of adrenal enkephalin secretion remains to be elucidated.
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Lim, Hye-Sun, Kyeong-No Yoon, Jin Ho Chung, Yong-Seok Lee, Dong Hun Lee, and Gunhyuk Park. "Chronic Ultraviolet Irradiation to the Skin Dysregulates Adrenal Medulla and Dopamine Metabolism In Vivo." Antioxidants 10, no. 6 (June 7, 2021): 920. http://dx.doi.org/10.3390/antiox10060920.
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Ultraviolet (UV) radiation has a strong biological effect on skin biology, and it switches on adaptive mechanisms to maintain homeostasis in organs such as the skin, adrenal glands, and brain. In this study, we examined the adaptation of the body to repeated bouts of UVB radiation, especially with respect to the catecholamine synthesis pathway of the adrenal glands. The effects of UVB on catecholamine-related enzymes were determined by neurochemical and histological analyses. To evaluate catecholamine changes after chronic excessive UVB irradiation of mouse skin, we examined dopamine and norepinephrine levels in the adrenal glands and blood from UV-irradiated and sham-irradiated mice. We found that chronic excessive UVB exposure significantly reduced dopamine levels in both tissues but did not affect norepinephrine levels. In addition, UVB irradiation significantly increased the levels of related enzymes tyrosine hydroxylase and dopamine-β-hydroxylase. Furthermore, we also found that apoptosis-associated markers were increased and that oxidative defense proteins were decreased, which might have contributed to the marked structural abnormalities in the adrenal medullas of the chronically UVB-irradiated mice. This is the first evidence of the damage to the adrenal gland and subsequent dysregulation of catecholamine metabolism induced by chronic exposure to UVB.
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Tischler, Arthur S., Karel Pacak, and Graeme Eisenhofer. "The Adrenal Medulla and Extra-adrenal Paraganglia: Then and Now." Endocrine Pathology 25, no. 1 (December 24, 2013): 49–58. http://dx.doi.org/10.1007/s12022-013-9286-3.
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Zheng, Huifei Sophia, Jeff Daniel, Chad David Foradori, Robert J. Kemppainen, and Chen-Che Jeff Huang. "Acute Transcriptional Effects of Dexamethasone on Mouse Adrenal Gland Transcriptome." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A65. http://dx.doi.org/10.1210/jendso/bvab048.131.
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Abstract Researchers have long known that dexamethasone causes cellular and functional changes in the adrenal gland. For example, long-term dexamethasone treatment leads to reversible adrenal cortex atrophy. In the adrenal medulla, dexamethasone treatment alters the maturation and function of the neural crest-derived chromaffin cells. Here we aim to study the acute transcriptional effect of dexamethasone on mouse adrenal gland at the transcriptome level. Our data suggested that a one-hour dexamethasone treatment had a cell type-specific effect on the adrenal transcriptome. There were 922 dexamethasone-induced genes and 853 dexamethasone-suppressed genes. GO analysis showed that the upregulated genes were primarily linked to neuronal cell function. Clustered heatmaps further showed that many genes involved in the catecholamine synthesis were upregulated by dexamethasone treatment, whereas most genes involved in the steroidogenesis pathway were downregulated. Interestingly, steroidogenic factor 1 (SF1, encoded by Nr5a1), the critical transcription factor that regulates steroidogenesis, had a >2-fold decrease under the one-hour dexamethasone treatment, suggesting a possible mechanism of the acute suppression of steroidogenic activity. Our findings indicate that the acute effects of dexamethasone stimulate catecholamine synthesis in the medulla, whereas steroidogenesis in the cortex is suppressed by dexamethasone.
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Morimoto, Ryo, Fumitoshi Satoh, Osamu Murakami, Takuo Hirose, Kazuhito Totsune, Yutaka Imai, Yoichi Arai, et al. "Expression of adrenomedullin 2/intermedin in human adrenal tumors and attached non-neoplastic adrenal tissues." Journal of Endocrinology 198, no. 1 (May 6, 2008): 175–83. http://dx.doi.org/10.1677/joe-08-0103.
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Adrenomedullin 2/intermedin (AM2/IMD) is a new member of calcitonin/calcitonin gene-related peptide family. AM is expressed in various tumors including adrenocortical tumors and modulates tumor growth. The AM2/IMD expression has not been studied, however, in adrenal tumors. The expression of AM2/IMD and AM was therefore studied in human adrenal tumors and attached non-neoplastic adrenal tissues by immunocytochemistry (ICC). Immunoreactive (IR)–AM2/IMD was measured by RIA. Furthermore, the expression of AM2/IMD and its receptor components, calcitonin receptor-like receptor (CRLR), and receptor activity-modifying proteins (RAMPs) 1, 2, and 3 mRNA in these tissues was studied by reverse transcription PCR (RT-PCR). ICC showed that AM2/IMD and AM immunoreactivities were localized in adrenocortical tumors and pheochromocytomas. AM2/IMD and AM immunoreactivities were detected in medulla of attached non-neoplastic tissues, while the degree of immunoreactivity for AM2/IMD and AM in cortices of attached adrenals was relatively weak or undetectable. RIA detected IR-AM2/IMD in adrenal tumors (0.414±0.12 to 0.786±0.27 pmol/g wet weight, mean±s.e.m.) and attached adrenal tissues (0.397±0.052 pmol/g wet weight). Reverse-phase high-performance liquid chromatography showed one broad peak eluted in the similar position to synthetic AM2/IMD with several minor peaks. RT-PCR showed expression of AM2/IMD, CRLR, and RAMP1, RAMP2, and RAMP3 mRNA in tissues of adrenal tumors and attached adrenal glands. In conclusion, AM2/IMD is expressed in human adrenal tumors and attached non-neoplastic adrenal tissues and may play (patho-)physiological roles in normal and neoplastic adrenals as an autocrine/paracrine regulator.
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Andreis, P. G., G. Neri, T. Prayer-Galetti, G. P. Rossi, G. Gottardo, L. K. Malendowicz, and G. G. Nussdorfer. "Effects of Adrenomedullin on the Human Adrenal Glands: An in Vitro Study." Journal of Clinical Endocrinology & Metabolism 82, no. 4 (April 1, 1997): 1167–70. http://dx.doi.org/10.1210/jcem.82.4.3854.
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Abstract Numerous lines of evidence indicate that adrenal medulla exerts a paracrine control on the secretory activity of the cortex by releasing catecholamines and several regulatory peptides. Adrenomedullin (ADM) is contained in adrenal medulla of several mammalian species, including humans. Thus, we investigated whether human ADM1–52 exerts a modulatory action on steroid secretion of human adrenal cortex in vitro. Dispersed adrenocortical cells (obtained from the gland tail deprived of chromaffin cells) and adrenal slices (including both capsule and medulla) were employed. ADM specifically inhibited angiotensin II-stimulated aldosterone secretion of dispersed cells and enhanced basal aldosterone production by adrenal slices, minimal effective concentrations being 10−7 and 10−9 mol/L, respectively. These effects of ADM were suppressed by the CGRP1 receptor antagonist CGRP8–37 (10−5 mol/L). Neither basal and ACTH-stimulated aldosterone secretion of dispersed cells nor agonist-enhanced aldosterone production by adrenal slices were affected by ADM, which also did not alter cortisol secretion of both types of adrenal preparations. ADM (10−6 mol/L) blunted the aldosterone secretagogue action of the Ca2+ ionophore A23187 (10−5 mol/L) on dispersed cells and adrenal slices. Theβ -adrenoceptor antagonist l-alprenolol (10−6 mol/L) suppressed aldosterone response of adrenal slices to 10−7 mol/L isoprenaline and ADM. ADM concentration dependently raised epinephrine and norepinephrine release by adrenal slices, minimal effective concentration being 10−9 mol/L. Collectively, these findings suggest that ADM, acting via the CGRP1 receptor subtype, exerts a direct inhibitory effect on angiotensin II-stimulated aldosterone secretion, which, when the integrity of adrenal tissue is preserved, is overcome and reversed by an indirect stimulatory action, conceivably involving the release of catecholamines by adrenal chromaffin cells.
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Jousselin-Hosaja, M. "Effects of transplantation on mouse adrenal chromaffin cells." Journal of Endocrinology 116, no. 1 (January 1988): 149—NP. http://dx.doi.org/10.1677/joe.0.1160149.
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ABSTRACT The effects of long-term transplantation on the ultrastructure of adrenaline- and noradrenaline-storing cells from the adrenal medulla were determined using morphometric methods. Mouse adrenal medulla were freed from the adrenal cortex and grafted into the occipital cortex of the brain. Two types of chromaffin cells were identified by electron microscopy in grafts fixed with glutaraldehyde and osmium tetroxide. Noradrenaline-type cells were predominant and formed 70–80% of the surviving population of grafted chromaffin cells. A minority of the chromaffin cells contained medium-sized granules (140–210 nm in diameter) (medium granule cell; MGC) with finely granular moderately electron dense cores. Morphometric analysis of noradrenaline phenotype cells and MGC cells in transplants showed no significant differences compared with the noradrenaline-storing cells of normal adrenal glands. In contrast, noradrenaline-type cells and MGC cells in the grafts had areas of secretory vesicles which were significantly (P<0·01) larger and areas of rough endoplasmic reticulum which were significantly (P<0 ·01) smaller than those of the adrenaline-storing cells of normal adrenal glands. It was concluded that long-term transplantation caused no degenerative changes in the ultrastructure of mouse adrenal chromaffin cells. J. Endocr. (1988) 116, 149–153
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Carter, A. M., B. S. Richardson, J. Homan, M. Towstoless, and J. R. Challis. "Regional adrenal blood flow responses to adrenocorticotropic hormone in fetal sheep." American Journal of Physiology-Endocrinology and Metabolism 264, no. 2 (February 1, 1993): E264—E269. http://dx.doi.org/10.1152/ajpendo.1993.264.2.e264.
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To determine whether adrenocorticotropic hormone (ACTH) at plasma concentrations measured during mild hypoxemia and at term affects adrenal blood flow, we measured regional blood flows in five unanesthetized normoxemic fetuses (125–130 days gestation) during a 24-h intravenous infusion of ACTH-(1–24) in isotonic saline solution. Another five fetuses received an infusion of vehicle. Blood flows were determined before the infusion, at 2 and 24 h from its onset, and 24 h afterward using radionuclide-labeled microspheres. Blood flow to the adrenal medulla was fivefold greater than that to the adrenal cortex. Adrenal blood flow rose 99% at 24 h of the ACTH infusion. There was a large increase in adrenal cortical blood flow of 272% at this time but medullary blood flow did not change significantly during ACTH infusion. The rise in cortical blood flow was attributable to decreased vascular resistance. No significant alterations occurred in fetal arterial blood pressure and heart rate, or in blood flow to other lower body organs of the fetus or to the placental cotyledons. These findings are consistent with the hypothesis that the increase in adrenal blood flow observed during fetal hypoxia is associated with changes in plasma ACTH concentration. They are also indicative of selective regulation of cortical and medullary blood flows in the sheep fetus at this stage of gestation.
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Rubello, D., C. Bui, D. Casara, MD Gross, LM Fig, and B. Shapiro. "Functional scintigraphy of the adrenal gland." European Journal of Endocrinology 147, no. 1 (July 1, 2002): 13–28. http://dx.doi.org/10.1530/eje.0.1470013.
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Over the last 30 years nuclear medicine imaging of the adrenal gland and its lesions has been achieved by the exploitation of a number of physiological characteristics of this organ. By seeking and utilising features which are quantitatively or qualitatively different from those of the adjacent tissues, functional depiction of the adrenal gland and its diseases, which in most cases retain the basic physiology of their tissue of origin, including both the cortex and the medulla, are now a useful clinical reality. Agents widely used in clinical practice include: (a) uptake and storage of radiolabelled cholesterol analogues via the low density lipoprotein (LDL) receptor and cholesterol ester storage pool in the adrenal cortex ((131)I-6-beta-iodomethyl-norcholesterol, (75)Se-selenomethyl-norcholesterol); (b) catecholamine type I, presynaptic, uptake mechanism and intracellular granule uptake and storage mechanism in the adrenal medulla and extra-adrenal paraganglia ((131)I-, (123)I- and (124)I-meta-iodo-benzyl-guanidine (MIBG), (18)F-metafluoro-benzyl-guanidine); (c) cell surface receptor binding of peptides/neurotransmitters/modulators such as for the family of five subtypes of somatostatin receptors ((123)I-tyr-octreotide, (111)In-DTPA-octreotide, (111)In-DOTA-octreotide and many others); (d) although not specific for the adrenal gland, increased glycolysis by tumours, particularly the most malignant varieties, (18)F-2-fluoro-d-deoxyglucose can thus be expected to depict certain malignant lesions such as malignant pheochromocytomas (particularly the minority which are not detected by MIBG) and adrenal incidentalomas (particularly when they occur in patients with known extra-adrenal malignancies). There are a variety of adrenal tissue characteristics with potential for exploitation but which are not currently in clinical use, and which may, nevertheless, have potential as imaging agents. These include: (a) inhibitors of adrenal cortical steroid hormone synthesis enzymes (e.g. radiolabelled analogues of metyrapone); (b) radiolabelled lipoproteins which bind to adrenocortical LDL receptors; (c) inhibitors of catecholamine biosynthesis enzymes (e.g. radiolabelled analogues of tyrosine and related amino acids); (d) cell surface receptors for various peptides and hormones which may be over-expressed on adrenal cortical or adrenal medullary tumours (e.g. radiolabelled analogues of ACTH on adrenocortical cells of zona fasciculata or zona glomerulosa origin, neurotransmitter/hormone message peptides binding to cell surface receptors such as bombesin, vasoactive intestinal polypeptide, cholecystokinin and opiate peptides); (e) the adrenal cortex can also synthesise cholesterol ab initio from acetate, and preliminary studies with (11)C-acetate positron emission tomography have shown interesting results.
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ADDICKS, K., G. HARTMANN, M. DONIKE, and W. SCHÄNZER. "Interaction between intracardiac sympathetic neurons and adrenal medulla." Acta Endocrinologica 116, no. 3_Suppl (August 1987): S39—S40. http://dx.doi.org/10.1530/acta.0.114s039.
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Gåfvels, M., S. Vilaró, and T. Olivecrona. "Lipoprotein lipase in guinea-pig adrenals: activity, mRNA, immunolocalization and regulation by ACTH." Journal of Endocrinology 129, no. 2 (May 1991): 213—NP. http://dx.doi.org/10.1677/joe.0.1290213.
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ABSTRACT Lipase activity in homogenates of guinea-pig adrenals was studied under conditions which exclude the hormone-sensitive lipase/cholesterol ester hydrolase. Antibody inhibition and chromatography on heparin–Sepharose showed that most of the activity was due to lipoprotein lipase (LPL), and that there was only a small amount of hepatic lipase activity. Northern blot analysis of total RNA demonstrated the same three adrenal LPL mRNA species (1·8, 3·1 and 3·5 kb) as were found in adipose tissue and heart. Hence, at least part of the LPL activity in adrenals is due to enzyme synthesized within the tissue. Immunolocalization showed that LPL was associated with the endothelium of blood vessels throughout the gland. In addition, there was cytoplasmic immunoreaction, suggesting that lipase was synthesized in a subpopulation of cells in the transitional zone between the fasciculata and reticularis layer of the cortex, particularly over lipid-filled cells. There was also intense immunofluorescence over scattered cells in the adrenal medulla. Treatment with an ACTH analogue depot (20 IU, i.m.) for 11 days induced a 12-fold increase in serum cortisol and increased adrenal weight 2·2-fold. The treatment induced increases in LPL mRNA (about twofold), LPL activity and in the number of cells in the adrenal cortex which gave an immunoreaction for LPL. Journal of Endocrinology (1991) 129, 213–220
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Mahata, Sushil K., Hong Zheng, Sumana Mahata, Xuefei Liu, and Kaushik P. Patel. "Effect of heart failure on catecholamine granule morphology and storage in chromaffin cells." Journal of Endocrinology 230, no. 3 (September 2016): 309–23. http://dx.doi.org/10.1530/joe-16-0146.
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One of the key mechanisms involved in sympathoexcitation in chronic heart failure (HF) is the activation of the adrenal glands. Impact of the elevated catecholamines on the hemodynamic parameters has been previously demonstrated. However, studies linking the structural effects of such overactivation with secretory performance and cell metabolism in the adrenomedullary chromaffin cells in vivo have not been previously reported. In this study, HF was induced in male Sprague-Dawley rats by ligation of the left coronary artery. Five weeks after surgery, cardiac function was assessed by ventricular hemodynamics. HF rats showed increased adrenal weight and adrenal catecholamine levels (norepinephrine, epinephrine and dopamine) compared with sham-operated rats. Rats with HF demonstrated increased small synaptic and dense core vesicle in splanchnic–adrenal synapses indicating trans-synaptic activation of catecholamine biosynthetic enzymes, increased endoplasmic reticulum and Golgi lumen width to meet the demand of increased catecholamine synthesis and release, and more mitochondria with dilated cristae and glycogen to accommodate for the increased energy demand for the increased biogenesis and exocytosis of catecholamines from the adrenal medulla. These findings suggest that increased trans-synaptic activation of the chromaffin cells within the adrenal medulla may lead to increased catecholamines in the circulation which in turn contributes to the enhanced neurohumoral drive, providing a unique mechanistic insight for enhanced catecholamine levels in plasma commonly observed in chronic HF condition.
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Coulter, C. L., I. R. Young, C. A. Browne, and I. C. McMillen. "Effect of hypophysectomy on the growth and development of the sheep adrenal gland: a morphometric study." Acta Endocrinologica 120, no. 3 (March 1989): 301–7. http://dx.doi.org/10.1530/acta.0.1200301.
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Abstract. We have investigated the effect of gestational age and fetal hypophysectomy on the growth and development of the adrenal gland of the fetal sheep. The area of the fetal sheep adrenal medulla increased significantly (P< 0.05) from 3.21 ± 0.42 mm2 at 90–107 days to 6.09 ± 0.26 mm2 at 120-126 days of gestation and there was a further significant increase (P< 0.05) in the newborn period to 9.48 ± 0.85 mm2. The adrenomedullary area of the hypophysectomised fetal sheep (7.47 ± 1.10 mm2) was not significantly different from that of the fetal sheep at 140–146 days of gestation or from that of the newborn lamb. The ratio of the area of the adrenal occupied by the cells which contained adrenaline (adrenaline zone) to the area of the adrenal occupied by the cells which contained noradrenaline (noradrenaline zone) was unchanged between 90 days of gestation and 12 days after birth. After hypophysectomy, the ratio of the adrenaline to noradrenaline zone was not significantly different from that in the adrenal medulla of the 140–146 days fetal sheep and the 10–12 days newborn lamb.
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Ho, M. M., and G. P. Vinson. "Endocrine control of the distribution of basic fibroblast growth factor, insulin-like growth factor-I and transforming growth factor-β1 mRNAs in adult rat adrenals using non-radioactive in situ hybridization." Journal of Endocrinology 144, no. 2 (February 1995): 379–87. http://dx.doi.org/10.1677/joe.0.1440379.
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Abstract This study located the particular cell types involved in the synthesis of growth factors in adult female rat adrenal glands. Non-isotopic in situ hybridization was used and the cellular localizations of the mRNAs of basic fibroblast growth factor (bFGF), IGF-I, and transforming growth factor-β1 (TGF-β1) were studied in adrenals from control animals and from those treated with ACTH or subjected to dietary sodium restriction. The adrenal medulla was the richest source of both bFGF and IGF-1 mRNA in both control and experimental rat adrenals. In the cortex, bFGF and IGF-I mRNAs were found mainly in the zona fasciculata in control animals, although some transcription was also detected in the zona reticularis and zona glomerulosa. Both ACTH and sodium restriction activated bFGF and IGF-I gene expression in the zona glomerulosa. Since cellular proliferation and differentiation occur primarily in the outer cortex, the data are consistent with the view that bFGF and IGF-I act as an autocrine/paracrine mitogen and differentiation regulator respectively in the rat adrenal cortex. Very small amounts of TGF-β1 mRNA were detected, predominantly in the zona fasciculata of control rats. There were no observable differences in amounts and localization of TGF-β1 mRNA between the adrenals of control rats and those treated with ACTH for 1 day. TGF-β1 mRNA was very weak or undetectable in the adrenals from rats treated with ACTH for three and five days or from sodium-restricted rats. Although TGF-β1 immunoreactive protein has been shown to be present in the zonae fasciculata and reticularis and to modulate negatively the steroidogenic activities in the adrenal cortex of other species, its gene is not actively expressed in rat adrenals. The present results showed that ACTH administration or dietary sodium restriction, both important adrenal mitogens in vivo, significantly altered the spatial patterns of the distribution of bFGF and IGF-I mRNAs and also increased the amount of bFGF mRNA in the adrenal cortex. This suggests that growth and differentiation of the adrenal cortex are partly mediated by bFGF and IGF-I. Journal of Endocrinology (1995) 144, 379–387
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Nakano, A., M. Terasawa, M. Watanabe, K. Okazaki, S. Inoue, M. Kato, Y. Nimura, N. Usuda, T. Morita, and H. Hidaka. "Distinct regional localization of neurocalcin, a Ca2+-binding protein, in the bovine adrenal gland." Journal of Endocrinology 138, no. 2 (August 1993): 283—NP. http://dx.doi.org/10.1677/joe.0.1380283.
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ABSTRACT Neurocalcin (molecular weight 23 000 and 24 000) is a Ca2+-binding protein with three putative Ca2+-binding domains and is present in large amounts in nervous tissues. Neurocalcin isoproteins separated by C18 reverse-phase column chromatography are insoluble in buffer solution and it is impossible to determine the dissociation constant of neurocalcin with Ca2+. To overcome this difficulty, recombinant neurocalcin was synthesized, based on one of the cDNAs of the neurocalcin isoproteins. Stoichiometric titration experiments, using recombinant neurocalcin, indicated that this protein bound 2 mol Ca2+/mol protein and that the apparent dissociation constant for Ca2+ was 2·2 μmol/l, suggesting that neurocalcin plays a physiological role in cellular function. Immunoblotting showed that neurocalcin is present in the bovine adrenal gland in addition to the nervous tissues. Neurocalcin, identified by immunoblotting, was purified from the bovine adrenal gland. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) of neurocalcin from the bovine brain showed 23 kDa and 24 kDa double bands, while SDS-PAGE of neurocalcin from the adrenal gland showed a single band of apparently 24 kDa, suggesting that the expression of neurocalcin isoproteins differs from tissue to tissue. The content of neurocalcin in the adrenal gland was 10 μg protein/100 g wet tissue. Immunohistochemical analysis showed the occurrence of neurocalcin in zona glomerulosa and adrenal medulla but not in zona fasciculata or zona reticularis. The restricted localization of neurocalcin in the adrenal gland suggests that a similar Ca2+ signal pathway may be present in zona glomerulosa and the adrenal medulla. Journal of Endocrinology (1993) 138, 283–290
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Spapen, Jerrold, Jeroen de Filette, Stijn Lochy, and Herbert Spapen. "Acute Heart Failure as a First Presentation of Pheochromocytoma Complicated with “Inverted” Takotsubo Syndrome." Case Reports in Endocrinology 2020 (March 17, 2020): 1–4. http://dx.doi.org/10.1155/2020/2521046.
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Takotsubo syndrome is a rare but emerging form of acute reversible myocardial injury characterized by transient systolic LV dysfunction, often related to emotional or physical stress. Pheochromocytoma is increasingly recognised as another possible trigger. Pheochromocytoma is a rare catecholamine-secreting tumour arising from chromaffin cells within the adrenal medulla or extra-adrenal paraganglia. The pathognomonic quartet of paroxysmal hypertension, palpitations, headache, and diaphoresis is rarely present, and diagnosis is often delayed. We describe a 43-year-old formerly healthy patient with an adrenal pheochromocytoma, presenting as an “inverted” takotsubo syndrome complicated with acute heart failure and pulmonary oedema.
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Ariznavarreta, C., M. D. Calderón, J. A. F. Tresguerres, and A. López-Calderón. "Effect of adrenomedullectomy and propranolol treatment on the response of gonadotrophins to chronic stress in male rats." Journal of Endocrinology 120, no. 2 (February 1989): 275–79. http://dx.doi.org/10.1677/joe.0.1200275.
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ABSTRACT In order to study the involvement of the adrenal medulla in stress-induced inhibition of gonadotrophin secretion, we measured plasma concentrations of LH, FSH and corticosterone in adult male rats subjected to chronic restraint after surgical ablation of the adrenal medulla. In intact animals, chronic restraint (6 h daily over 4 days) induced a significant (P<0.05) decrease in plasma concentrations of LH, whereas plasma concentrations of corticosterone showed the expected significant (P<0.01) increase. Adrenomedullectomy did not significantly modify basal plasma concentrations of LH or corticosterone. In these rats, there was no significant decrease of LH after stress, while the increase in corticosterone was as significant as in sham-operated animals (P<0.01). In order to confirm the role of adrenomedullary catecholamines in stress-induced gonadotrophin inhibition another group of rats was treated s.c. with the β-adrenergic blocker propranolol (2 mg/kg twice daily). These rats showed an attenuated inhibition of LH during stress similar to that observed in adrenomedullectomized rats. Levels of FSH were significantly reduced after stress in the saline-treated group, while there were no differences between stressed or unstressed rats in the propranolol-treated group. These results may be considered as evidence that medullary catecholamines, acting through β-receptors, are factors involved in gonadotrophin inhibition during chronic stress. Journal of Endocrinology (1989) 120, 275–279
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Grazzini, E. "Vasopressin Receptors in Human Adrenal Medulla and Pheochromocytoma." Journal of Clinical Endocrinology & Metabolism 84, no. 6 (June 1, 1999): 2195–203. http://dx.doi.org/10.1210/jc.84.6.2195.
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Vatta, M. S., L. G. Bianciotti, A. S. Locatelli, M. L. Papouchado, and B. E. Fernández. "Monophasic and biphasic effects of angiotensin II and III on norepinephrine uptake and release in rat adrenal medulla." Canadian Journal of Physiology and Pharmacology 70, no. 6 (June 1, 1992): 821–25. http://dx.doi.org/10.1139/y92-110.
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Angiotensin II and III have hypertensive effects. They induce vascular smooth muscle constriction, increase sodium reabsorption by renal tubules, stimulate the anteroventral third ventricle area, increase vasopressin and aldosterone secretions, and modify catecholamine metabolism. In this work, angiotensin II and III effects on norepinephrine uptake and release in rat adrenal medulla were investigated. Both angiotensins decreased total and neuronal norepinephrine uptake. Angiotensin II showed a biphasic effect only on evoked neuronal norepinephrine release (an earlier decrease followed by a later increase), while increasing the spontaneous norepinephrine release only after 12 min. On the other hand, angiotensin III showed a biphasic effect on evoked and spontaneous neuronal norepinephrine release. Both angiotensins altered norepinephrine distribution into intracellular stores, concentrating the amine into the granular pool and decreasing the cytosolic store. The results suggest a physiological biphasic effect of angiotensin II as well as angiotensin III that may be involved in the modulation of sympathetic activity in the rat adrenal medulla.Key words: angiotensin II, angiotensin III, norepinephrine uptake, norepinephrine release, adrenal medulla.
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Nonaka, K., Junko Aida, Kaiyo Takubo, Yuto Yamazaki, Xin Gao, Akiko Komatsu, Shoichiro Takakuma, et al. "Correlation Between Telomere Attrition of Zona Fasciculata and Adrenal Weight Reduction in Older Men." Journal of Clinical Endocrinology & Metabolism 105, no. 3 (October 9, 2019): e200-e210. http://dx.doi.org/10.1210/clinem/dgz214.
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Abstract Context Although numerous theories are reported on sex differences in longevity, the underlying biological mechanisms remain unknown. We previously reported that telomere length in the zona reticularis cells of the human adrenal cortex was significantly longer in older than that in younger subjects. However, we could not evaluate sex differences in the telomere lengths. Objective To compare the telomere lengths of adrenocortical and adrenal medullar cells between men and women from infancy through older adulthood. Methods Adrenal glands of 30 male (aged 0 to 100 years) and 25 female (aged 0 to 104 years) autopsied subjects were retrieved from autopsy files. Using quantitative fluorescence in situ hybridization, relative telomere lengths were determined in the parenchymal cells of the 3 adrenocortical zones and medulla. Age-related changes in the weight of adrenal glands were also investigated. Main results Older male subjects (aged 65 years or older) had significantly shorter telomere lengths in zona fasciculata (ZF) cells compared to the corresponding female subjects. In men, older subjects exhibited a significant age-related reduction in adrenal weight; however, no age-related changes in adrenal weight were detected in women. Conclusion Telomere attrition of ZF cells was correlated with adrenal weight reduction in older men but not in older women, suggesting a decreased number of ZF cells in older men. This may help us understand the possible biological mechanisms of sex difference in longevity of humans.
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Fallo, Francesco, Matteo Pistorello, Francesco Pedini, Domenico D'Agostino, Franco Mantero, and Marco Boscaro. "In vitro evidence for local generation of renin and angiotensin II/III immunoreactivity by the human adrenal gland." Acta Endocrinologica 125, no. 3 (September 1991): 319–30. http://dx.doi.org/10.1530/acta.0.1250319.
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Abstract. The adrenal gland of various mammalian species has been shown to contain all the components of a functional renin-angiotensin system. We investigated the existence of this local system in human adrenal tissues surgically obtained. Eight normal adrenals (cortex and medulla) and 6 aldosterone-producing adenomas (aldosteronomas) were examined. Minced tissues were superfused over 270 min, and 15-min fractions were collected. In the perfusates, active renin was measured by immunoradiometric assay with human anti-renin monoclonal antibodies; immunoreactive angiotensin II/III and aldosterone were measured by radioimmunoassay. Adrenal tissues, either normal or pathological, were found concomitantly to release renin, angiotensin II/III and aldosterone. The pattern of this spontaneous release exhibited a pulsatile character. The total amount of renin and angiotensin II/III secreted during superfusion clearly exceeded the tissue content (determined by extraction). Addition of the angiotensin-converting enzyme inhibitor quinaprilat (4×10−5 mol/l) in the superfusion caused a concomitant decrease of angiotensin II/III and aldosterone secretion by 3 normal tissues, and no change in 2 aldosteronomas. These data provide evidence that the human adrenal gland in vitro generates and releases both renin and angiotensin II/III, and support the hypothesis that locally formed angiotensin II/III may play a role as a paracrine regulator of physiological aldosterone secretion.
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Anouar, Youssef, Christine Desmoucelles, Laurent Yon, Jerome Leprince, Lyne Breault, Nicole Gallo-Payet, and Hubert Vaudry. "Identification of a Novel Secretogranin II-Derived Peptide (SgII187–252) in Adult and Fetal Human Adrenal Glands Using Antibodies Raised against the Human Recombinant Peptide1." Journal of Clinical Endocrinology & Metabolism 83, no. 8 (August 1, 1998): 2944–51. http://dx.doi.org/10.1210/jcem.83.8.5009.
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abstract Molecular cloning of secretogranin II (SgII) in phylogenetically distant species has recently revealed the existence of a highly conserved 66-amino acid peptide flanked by preserved pairs of basic residues. This observation suggested that this peptide, named EM66, which had not been described to date, could be an important processing product of SgII. The aim of the present study was to investigate the possible occurrence of EM66 in the human adrenal gland. The EM66 peptide was generated in Escherichia coli, which was programmed to make a fusion protein containing the human EM66 sequence. The affinity-purified fusion protein was used to raise polyclonal antibodies in rabbits. The free EM66 peptide was obtained by cleavage of the fusion protein followed by high performance liquid chromatography purification. Immunohistochemical analysis using the EM66 antibodies revealed intense labeling of adrenochromaffin cells in the adult adrenal medulla and the fetal adrenal gland. A sensitive and specific RIA was developed and applied to the detection of EM66-like immunoreactivity in extracts of adult adrenal medulla and whole fetal adrenal gland after high performance liquid chromatographic analysis. A major immunoreactive species exhibiting the same retention time as recombinant EM66 was detected in both adult and fetal adrenal extracts. Taken together, these data demonstrate that posttranslational processing of SgII actually generates EM66 in the adrenal gland. The strong conservation of the amino acid sequence of EM66 in the vertebrate phylum and the occurrence of the mature peptide in both fetal and adult chromaffin cells suggest that EM66 could play an important physiological role in the human adrenal gland.
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Barrera, Francisco, Luis Borges Espinosa, and Alejandro Ayala. "PSAT013 Elevated Plasma Free Metanephrines with No Evidence of Pheochromocytoma in a Patient with Multiple Endocrine Neoplasia Type 2A." Journal of the Endocrine Society 6, Supplement_1 (November 1, 2022): A92—A93. http://dx.doi.org/10.1210/jendso/bvac150.189.
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Abstract Background Adrenal medullary hyperplasia (AMH) is arbitrarily defined by adrenal medullary proliferation measuring less than 1 cm while larger lesions are considered pheochromocytoma. Some patients with MEN2 present with adrenal medullary hyperplasia (AMH), which is a precursor of pheochromocytomas. Clinical Case A 22-year-old female with a past medical history of MEN2A. She is positive for germline mutation in RET proto-oncogene at 10q11.2 exon 11, position 634 from cysteine to arginine. She was evaluated for a 1cm left thyroid nodule, which required total thyroidectomy for Medullary Thyroid Cancer. Pathology revealed a 0.5cm deposit on the largest dimension, clear margins, and no angiovascular, or lymphovascular invasion, surgery was complicated by hypoparathyroidism. She complained of intermittent anxiety and fatigue but was otherwise asymptomatic. Physical examination is unremarkable except for thyroidectomy scar and multiple exostoses. On 8/5/2011 plasma-free metanephrines were elevated at 83 pg/ml (<57pg/ml) and Free normetanephrine was 45 pg/ml (<145pg/ml). Over the next years, her plasma-free metanephrine levels have been checked approximately every 6 months ranging between 63-106pg/ml with free plasma normetanephrine in normal ranges (30-81pg/ml). However, on 2/2021, her plasma normetanephrine level increased to 304pg/ml. More recently, on 11/30/2021 her free normetanephrine levels reached 671pg/ml and free Metanephrine 131pg/ml. She had two MRIs of the abdomen and pelvis over the years and both showed unremarkable adrenal glands. NM I-123 MIBG scintigraphy reported physiologic symmetric activity in the adrenal glands. Finally, she had GA-68 DOTATATE PET/CT with no suspicious radiotracer avid lesion in the abdominopelvic organs. Given the persistent elevation on plasma metanephrines, we decided to start the patient on Doxazosin prophylactically while we continue biochemical and imaging surveillance. Conclusion Our patient has a persistent elevation in plasma-free metanephrines with no evidence of pheochromocytoma in abdominal imaging. The earliest abnormality in the adrenal medulla in patients with MEN 2 is diffuse hyperplasia with a reduction in the cortical/medullary ratio (1). This hyperplasia is considered to be a precursor of pheochromocytoma in patients with MEN 2 and in our case the most likely explanation for the progressive elevation in plasma-free metanephrines (1). There is a strong molecular relationship between AMH and Pheochromocytoma (2), close monitoring for progression to pheochromocytoma is necessary for all patients with AMH. The presence of markedly elevated plasma metanephrines in an asymptomatic patient with no evidence of pheochromocytoma poses a therapeutic dilemma for preemptive use of alpha blockade and the potential need for a medical alert bracelet. References (1) Cho, K et al "Adrenal Medullary disease in Multiple Endocrine Neoplasia II". AJR 134: 23-29. (2) Korpershoek, E et al "Adrenal Medullary Hyperplasia Is a Precursor Lesion for Pheochromocytoma in MEN2 Syndrome". Neoplasia. 2014 Oct; 16(10): 868–873 Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
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Andreazzi, Ana Eliza, Sabrina Grassiolli, Paula Beatriz Marangon, Adriana Gallego Martins, Júlio Cézar de Oliveira, Rosana Torrezan, Clarice Gravena, Raúl Marcel González Garcia, and Paulo Cezar de Freitas Mathias. "Impaired Sympathoadrenal Axis Function Contributes to Enhanced Insulin Secretion in Prediabetic Obese Rats." Experimental Diabetes Research 2011 (2011): 1–11. http://dx.doi.org/10.1155/2011/947917.
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The involvement of sympathoadrenal axis activity in obesity onset was investigated using the experimental model of treating neonatal rats with monosodium L-glutamate. To access general sympathetic nervous system activity, we recorded the firing rates of sympathetic superior cervical ganglion nerves in animals. Catecholamine content and secretion from isolated adrenal medulla were measured. Intravenous glucose tolerance test was performed, and isolated pancreatic islets were stimulated with glucose and adrenergic agonists. The nerve firing rate of obese rats was decreased compared to the rate for lean rats. Basal catecholamine secretion decreased whereas catecholamine secretion induced by carbachol, elevated extracellular potassium, and caffeine in the isolated adrenal medulla were all increased in obese rats compared to control. Both glucose intolerance and hyperinsulinaemia were observed in obese rats. Adrenaline strongly inhibited glucose-induced insulin secretion in obese animals. These findings suggest that low sympathoadrenal activity contributes to impaired glycaemic control in prediabetic obese rats.
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Eckardt, Luise, Maria Prange-Barczynska, Emma J. Hodson, James W. Fielding, Xiaotong Cheng, Joanna D. C. C. Lima, Samvid Kurlekar, Gillian Douglas, Peter J. Ratcliffe, and Tammie Bishop. "Developmental role of PHD2 in the pathogenesis of pseudohypoxic pheochromocytoma." Endocrine-Related Cancer 28, no. 12 (December 1, 2021): 757–72. http://dx.doi.org/10.1530/erc-21-0211.
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Despite a general role for the HIF hydroxylase system in cellular oxygen sensing and tumour hypoxia, cancer-associated mutations of genes in this pathway, including PHD2, PHD1, EPAS1 (encoding HIF-2α) are highly tissue-restricted, being observed in pseudohypoxic pheochromocytoma and paraganglioma (PPGL) but rarely, if ever, in other tumours. In an effort to understand that paradox and gain insights into the pathogenesis of pseudohypoxic PPGL, we constructed mice in which the principal HIF prolyl hydroxylase, Phd2, is inactivated in the adrenal medulla using TH-restricted Cre recombinase. Investigation of these animals revealed a gene expression pattern closely mimicking that of pseudohypoxic PPGL. Spatially resolved analyses demonstrated a binary distribution of two contrasting patterns of gene expression among adrenal medullary cells. Phd2 inactivation resulted in a marked shift in this distribution towards a Pnmt−/Hif-2α+/Rgs5+ population. This was associated with morphological abnormalities of adrenal development, including ectopic TH+ cells within the adrenal cortex and external to the adrenal gland. These changes were ablated by combined inactivation of Phd2 with Hif-2α, but not Hif-1α. However, they could not be reproduced by inactivation of Phd2 in adult life, suggesting that they arise from dysregulation of this pathway during adrenal development. Together with the clinical observation that pseudohypoxic PPGL manifests remarkably high heritability, our findings suggest that this type of tumour likely arises from dysregulation of a tissue-restricted action of the PHD2/HIF-2α pathway affecting adrenal development in early life and provides a model for the study of the relevant processes.
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Emuze, Martins Ehizode, Arinola Esan, Jokotade Adeleye, Marcus O. Ifeh, Augustine Takure, Temilola Akande, William Balogun, and Abimbola Olukayode Lawal. "Extra-adrenal phaeochromocytoma in a resource poor setting: A case report." Endocrine Regulations 56, no. 1 (January 1, 2022): 48–54. http://dx.doi.org/10.2478/enr-2022-0006.
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Abstract Phaeochromocytomas are catecholamine-secreting tumors arising in the chromaffin cells of the adrenal medulla. They are a rare cause of secondary hypertension. However, catecholamine secreting tumors may also be found in the extra-adrenal sites, producing similar symptoms as the adrenal phaeochromocytoma. The extra-adrenal phaeochromocytomas, are referred to as paragangliomas (PGLs). About 75% of extra-adrenal phaeochromocytomas are intra-abdominal, mostly located in perinephric, periaortic, and bladder regions. Most phaeochromocytomas secrete excessive amount of epinephrine and norepinephrine, whereas most paragangliomas secrete only norepinephrine. The excessive secretion of these products could lead to paroxysms of symptoms that could be life threatening. Medical management is initially offered, but definitive treatment involves surgical removal of the tumor, which requires promptness on the both the clinician and the patient sides. We present a case of an extra-adrenal phaeochromocytoma in an adult male with revealing imaging of a mass surrounding the bladder. The patient was managed with both alpha- and beta-adrenergic blockers. He declined the surgery and eventually died after appearing in an acute hypertensive crisis.
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Coulter, C. L., I. R. Young, C. A. Browne, and I. C. McMillen. "The effect of fetal hypophysectomy with or without ACTH replacement on the molecular weight profile of enkephalin-containing peptides in the adrenal medulla of the fetal sheep." Journal of Endocrinology 134, no. 3 (September 1992): 369–75. http://dx.doi.org/10.1677/joe.0.1340369.
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ABSTRACT We have investigated the possible role of the fetal pituitary and ACTH in the control of the synthesis and post-translational processing of the enkephalin precursor, proenkephalin A (proEnk A), in the fetal sheep adrenal gland in late gestation. Fetal hypophysectomy (n = 8) or sham operations (n = 4) were performed between 109 and 118 days of gestation. At 138–139 days, either ACTH(1–24) (10·5 μg/0·24 ml saline per h, n = 4) was infused intravenously for 72 h into hypophysectomized fetal sheep or 0·9% (w/v) NaCl alone (0·24 ml/h, n = 4) was infused for 72 h into hypophysectomized fetal sheep and sham-operated animals. At the end of the infusion the pregnant ewe was killed and left or right adrenal glands (n = 12) were collected from the fetal sheep that were intact and given saline (Intact + sal; n = 4), hypophysectomized and given saline (Hx + sal; n = 4) and hypophysectomized and given ACTH (Hx + ACTH; n = 4). Each adrenal was homogenized in acid (acetic acid (1 mol/l)/HCl (20 mmol/l)/2-mercaptoethanol (0·2%)). After centrifugation, the supernatant was loaded onto a Sephadex G-75 column (2·0 × 50 cm), eluted at 80 ml/24 h and fractions were collected (5 ml, n = 42). An aliquot of each fraction (2 ml) was dried down prior to enzymatic digestion (trypsin/carboxypeptidase B) and oxidation with H2O2, and assay for methionine-O-enkephalin (immunoreactive Met-O-Enk). The total adrenal content of immunoreactive Met-O-Enk was significantly greater in the Hx + ACTH group (326·2 ±66·7 (s.e.m.)ng/adrenal) when compared with either the Intact + sal group (152·7 ±44·0 ng/adrenal) or the Hx + sal group (112·1 ±20·8 ng/adrenal). In the adrenal glands from all fetuses immunoreactive Met-O-Enk was found in four molecular weight ranges: < 12 kDa, 12–7 kDa, 7–3 kDa and < 3 kDa. There was no significant difference between the Hx + sal and Hx + ACTH groups in the proportion of immunoreactive Met-O-Enk present in each of the molecular weight ranges in the adrenals and therefore the data from these groups were combined for further statistical analysis. The proportion of immunoreactive Met-O-Enk in the > 12 kDa range was significantly less in the Intact + sal group (5·5 ±2·3%) when compared with the hypophysectomized sheep with or without ACTH replacement (18·7 ± 4·5%). These data demonstrate that fetal hypophysectomy alters the molecular weight profile of Enk-containing peptides in the adrenal of the fetal sheep and whilst ACTH replacement in the hypophysectomized fetus does not alter the post-translational processing of the Enk-containing peptides, it stimulates an increase in the total amount of immunoreactive Met-O-Enk in the fetal adrenal in late gestation. Journal of Endocrinology (1992) 134, 369–375
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Ilias, I., and K. Pacak. "Diagnosis and Management of Tumors of the Adrenal Medulla." Hormone and Metabolic Research 37, no. 12 (December 2005): 717–21. http://dx.doi.org/10.1055/s-2005-921091.
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Korpershoek, Esther, Bart-Jeroen Petri, Francien H. van Nederveen, Winand N. M. Dinjens, Albert A. Verhofstad, Wouter W. de Herder, Sonja Schmid, Aurel Perren, Paul Komminoth, and Ronald R. de Krijger. "Candidate gene mutation analysis in bilateral adrenal pheochromocytoma and sympathetic paraganglioma." Endocrine-Related Cancer 14, no. 2 (June 2007): 453–62. http://dx.doi.org/10.1677/erc-06-0044.
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Pheochromocytomas (PCCs) are rare tumors that arise from chromaffin tissue in the adrenal medulla, but can also occur in the abdomen outside the adrenals and are then called sympathetic paragangliomas (sPGLs). According to the literature, between 15 and 25% of apparently sporadic adrenal PCC and sPGL are caused by germline mutations in RET, von Hippel–Lindau disease (VHL), succinate dehydrogenase subunit B (SDHB), or subunit D SDHD. However, few studies have addressed the mutationfrequency of these candidate genes in selected subgroups of PCC andsPGL, such as bilateral adrenal PCC or extra-adrenal sPGL, and none have looked at somatic mutations by analyzing tumor tissue. Therefore, we have investigated the occurrence of germline and somatic mutations in RET, VHL, SDHB, and SDHD in comparatively large series of bilateral adrenal PCC (n = 33 patients) and sPGL (n = 26 patients), with the aim of determining the mutation frequency of each of these genes and to establish a genetic testing algorithm. Twenty-one RET, two VHL germline, and one SDHD mutations were found in the patients with bilateral adrenal PCC. In sPGL, one novel SDHB germline and one novel SDHB somatic mutation were observed. In addition, two SDHD germline mutations were found. We conclude that germline RET mutations are predominantly found in bilateral PCC, and that somatic and germline SDHB and SDHD mutations usually occur in sPGL, which has practical consequences for genetic testing algorithms. We suggest that sequential mutation analysis should be directed first at RET, followed by VHL and SDHD for patients with bilateral adrenal PCC at diagnosis, and at SDHB and SDHD for patients with sPGL.
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D'Amato, Filomena, Barbara Noli, Carla Brancia, Cristina Cocco, Giovanna Flore, Maria Collu, Paola Nicolussi, and Gian-Luca Ferri. "Differential distribution of VGF-derived peptides in the adrenal medulla and evidence for their selective modulation." Journal of Endocrinology 197, no. 2 (February 13, 2008): 359–69. http://dx.doi.org/10.1677/joe-07-0346.
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While vg f gene knockout mice are hyperactive and hypermetabolic, surprisingly the TLQP-21 brain VGF peptide increased energy consumption, suggesting that opposing regulatory effects could be exerted by peptides alternatively cleaved from the VGF precursor. Using antisera to the VGF precursor C-terminus and three cleavage products, we revealed a distinct differential distribution in adrenal, certain peptides (VGF422–430: PGH peptides) being found throughout bovine and swine medulla, while C-terminus and TLQP peptides were confined to adrenaline cells in the above species and in rat and C-terminally shortened forms (VGF604–612: HVLL peptides) to nor-adrenaline cells. Random abattoir samples of bovine and swine adrenal contained 520±40 and 450±60 pmol/g (mean±s.e.m. respectively) of C-terminus peptides and similar or lower amounts of others. Upon gel chromatography, bona fide VGF precursor, ~7.5 and ~3.5 kDa forms were revealed by C-terminus assays, HVLL peptides being limited to small fragments. TLQP peptides included ~7.5 kDa form and peaks accounting for TLQP-21 and predicted TLQP-30 and TLQP-42. Low molecular weight (MW) PGH peptides were revealed, together with a high MW form possibly encompassing the VGF precursor N-terminus. In acutely stressed swine, a striking increase was seen for C-terminus and TLQP peptides, with no significant differences for PGH peptides. A similar response was found in rat TLQP peptides showing a major increase upon an acute swimming stress and 30 min thereafter. A differential processing of the VGF precursor encompassing many areas of its primary sequence and selective modulations of its derived peptides occur in adrenal medullary cells, possibly relevant to adaptive homeostatic responses.
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Chiu, Christine E., and Trevor E. Angell. "Catecholamine-Producing Adrenal Schwannoma: A Rare Pheochromocytoma Imposter." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A123—A124. http://dx.doi.org/10.1210/jendso/bvab048.248.
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Abstract Background:Adrenal schwannoma is a tumor of the adrenal medulla that poses a pre-operative diagnostic challenge due to its non-specific imaging findings and rarity. Even more uncommon are functional catecholamine-producing adrenal schwannomas (CPAS) that can lead to the clinical presentation of catecholamine excess. Here, we present a case of biochemically and histopathologically confirmed CPAS and provide a review of the existing cases in the literature. Clinical Case: A 43-year old woman with a history of hypertension was incidentally found to have a 4 cm left adrenal lesion. Computed tomography of the mass demonstrated indeterminate enhancement and washout characteristics. Upon evaluation, she had episodes of palpitations and fatigue without headache or flushing. Her medications were notable for metoprolol, vortioxetine, and lisdexamfetamine. Laboratory results were notable for elevated 24-hour urine metanephrine and normetanephrine of 551 mcg/24hr (normal: 58–203 mcg/24hr) and 927 mcg/24hr (normal: 88–649 mcg/24hr) respectively. Due to the possibility of pheochromocytoma, the patient elected for surgery and underwent laparoscopic left adrenalectomy after pre-treatment with an alpha-1-antagonist. Pathology demonstrated a 4.8 cm well-circumscribed tumor arising from the adrenal medulla that showed mostly hypercellular areas of spindled cells with wavy nuclei and focal nuclear palisading along with hypocellular areas with loose edematous stroma with focal areas of calcification and microcyst formation. IHC of the tumor cells was diffusely positive for S-100 and SOX-10, consistent with adrenal schwannoma. Laboratory results approximately 2 months post-operative on the same medications demonstrated normalization of 24-hour urine metanephrine and normetanephrine, confirming CPAS. A search of PubMed was performed using the search terms “adrenal schwannoma,” which returned 41 reports, of which 2 confirmed CPAS. Of the 3 cases, including ours, patients had a mean age of 44 years old and M:F ratio of 1:2. Each of the 3 tumors were left-sided with sizes ranging from 4.8 cm to 7.7 cm, which were all surgically removed. In the two previously published reports, the reported pre-operative laboratory markers were serum catecholamines and urine catecholamines, respectively, but neither compared levels to a reference range. In all cases, catecholamine levels normalized following surgical removal. Conclusion: Adrenal schwannoma is a rare entity in the differential diagnosis of non-functioning adrenal incidentaloma, but it should be considered for catecholamine-producing adrenal tumors as well. A summary of published cases suggests that these are typically large tumors with possible female predominance. This case is the first to document levels of catecholamine metabolite concentrations in CPAS.
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Zajicek, G., I. Ariel, and N. Arber. "The streaming adrenal cortex: direct evidence of centripetal migration of adrenocytes by estimation of cell turnover rate." Journal of Endocrinology 111, no. 3 (December 1986): 477–82. http://dx.doi.org/10.1677/joe.0.1110477.
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ABSTRACT Thirty adult male rats were injected with 0·5 μCi [3H]thymidine/g body weight (specific activity 5 Ci/ mmol) and killed, in groups of five, 1 h and 14, 30, 60, 90 and 120 days after injection. The displacement of labelled adrenocytes with time was estimated in autoradiograms of adrenal sections. The radial distance of the labelled cell from the capsule was measured with an eyepiece micrometer and expressed in cell location units, i.e. the number of cells separating the labelled cell from the capsule. One hour after labelling, 95% of labelled cells were confined to the outer quarter of the cortex. During the following days, adrenocytes were displaced inwardly, approaching the medulla at a velocity of 0·24 locations/day. They traversed the three cortex zones, reaching the medulla after 104 days. The three adrenal zones represent three differentiation states of the adrenocyte. When young, the adrenocyte secretes aldosterone, after leaving the glomerulosa it produces corticosteroids and on reaching the reticularis it produces sex hormones. The adrenal cortex is a cell renewal system made of two compartments. A progenitor compartment extending between locations 1 and 15, and a functional compartment, covering locations 16–64. The first compartment produces 0·47 cells daily, which enter the second. Half of them die on their way while the rest are eliminated in the reticular zone. The cell stream is nourished by a subcapsular stem cell. J. Endocr. (1986) 111, 477–482
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KIHARA, K., K. SATO, and H. OSHIMA. "Involvement of the adrenal medulla in ejaculatory reactions in the dog." International Journal of Andrology 20, no. 2 (July 1997): 104–11. http://dx.doi.org/10.1046/j.1365-2605.1997.00041.x.
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