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Journal articles on the topic 'Pregnenolone'

Author: Grafiati

Published: 4 June 2021

Last updated: 19 February 2022

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1

McKay, S. A., G. Jenkin, and G. D. Thorburn. "Peripheral plasma concentrations of pregnenolone sulphate, pregnenolone, progesterone and 20α-hydroxy-4-pregnen-3-one in ewes throughout the oestrous cycle." Journal of Endocrinology 113, no. 2 (May 1987): 231–37. http://dx.doi.org/10.1677/joe.0.1130231.

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ABSTRACT Pregnenolone sulphate, pregnenolone, progesterone and 20α-hydroxy-4-pregnen-3-one concentrations in peripheral plasma of normal cyclic ewes were measured by radioimmunoassay. The concentrations of these steroids were correlated with that of progesterone. The concentrations of all the steroids measured in peripheral plasma varied in a cyclic manner and showed a significant (P <0·05) positive correlation with the concentration of progesterone. Peripheral plasma concentrations of these steroids in ovariectomized and ovariectomized, dexamethasone-treated ewes were also determined. The plasma concentration of progesterone in ovariectomized ewes was undetectable but the concentrations of pregnenolone sulphate, pregnenolone and 20α-hydroxy-4-pregnen-3-one remained similar to those observed at oestrus. Administration of dexamethasone to ovariectomized ewes had no effect on pregnenolone sulphate or pregnenolone concentrations but 20α-hydroxy-4-pregnen-3-one concentrations, which were already very low, decreased further. It is proposed that the ovary, probably the corpus luteum, secretes pregnenolone sulphate, pregnenolone and 20α-hydroxy-4-pregnen-3-one; however, pregnenolone sulphate and 20α-hydroxy-4-pregnen-3-one may also arise from the metabolism of circulating pregnenolone and progesterone. J. Endocr. (1987) 113, 231–237.

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2

Tsang, Benjamin K., David F. Mattice, Ming Li, and Elikplimi K. Asem. "Effect of calcium ionophore A23187 on pregnenolone metabolism to progesterone in rat granulosa cells." Canadian Journal of Physiology and Pharmacology 66, no. 7 (July 1, 1988): 960–63. http://dx.doi.org/10.1139/y88-157.

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The effect of calcium ionophore A23187 on the metabolism of pregnenolone to progesterone was examined in rat granulosa cells during a 24-h culture period. Granulosa cells harvested from pregnant mare's serum gonadotropin treated immature rats were incubated in the presence and absence of the divalent cation ionophore A23187. The ionophore induced progesterone synthesis from both endogenous sterol substrate and exogenous pregnenolone in a time- and concentration-dependent manner. Pregnenolone metabolism was examined in the presence of aminoglutethimide phosphate, an inhibitor of endogenous pregnenolone production. Steroid secretion resulting from metabolism of endogenous substrate was more sensitive to A23187 in that a lower concentration of the ionophore was required to induce a significant increase than that noted for exogenous pregnenolone metabolism. In addition, progesterone production from endogenous sterol occurred 6 h earlier than the observed increase in the conversion of pregnenolone to progesterone. These results indicate that A23187 and therefore possibly enhanced calcium influx may play a significant role in the regulation of pregnenolone metabolism in granulosa cells depending on the duration of incubation. The earlier steroidogenic response from endogenous substrate may be a reflection of an acute effect of A23187 on certain steroidogenic steps proximal to pregnenolone production.

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3

Tian, Yuan, Yang Hong, Samuel J. Bonacorsi, Aaron Balog, and Sharon Gong. "Synthesis of [3α-3H] 17α-Hydroxy pregnenolone and [3α-3H] Pregnenolone." Journal of Labelled Compounds and Radiopharmaceuticals 57, no. 1 (October 24, 2013): 1–11. http://dx.doi.org/10.1002/jlcr.3114.

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4

Jiang, Jingjing, Xue Liu, Xiaotian Liu, Zhongyan Tian, Haiqing Zhang, Xinling Qian, Zhicheng Luo, et al. "The effect of progesterone and pregnenolone on diabetes status in Chinese rural population: a dose–response analysis from Henan Rural Cohort." European Journal of Endocrinology 181, no. 6 (December 2019): 603–14. http://dx.doi.org/10.1530/eje-19-0352.

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Objective Previous studies have uncovered a progestin-only contraceptive association with an increased risk of diabetes, but limited studies have explored the relationship of endogenous progesterone and pregnenolone levels with diabetes status. A case–control study was conducted in Henan Rural Cohort (register number: ChiCTR-OOC-15006699) to evaluate the dose–response independent and interactive relationship of progesterone and pregnenolone levels with prediabetes and type 2 diabetes mellitus (T2DM) in Chinese rural population. Design A case-control study. Methods A total of 798 T2DM patients, 779 prediabetes patients, and 782 individuals with normal fasting plasma glucose were included in this study. Serum progesterone and pregnenolone were detected by liquid chromatography-tandem mass spectrometry. Logistic regression and restricted cubic splines were used to assess the independent effects of progesterone and pregnenolone on prediabetes and T2DM. Interactive plots were employed to examine the interaction effects of progesterone and pregnenolone. Results Progesterone in the fourth versus first quartile was positively associated with prediabetes (odds ratio (OR) (95% CI): 2.66 (1.99–3.55)) and T2DM (OR (95% CI): 6.41 (4.57–8.98)), whereas pregnenolone in the fourth versus first quartile was inversely related to prediabetes (OR (95% CI): 0.23 (0.16–0.33)) and T2DM (OR (95% CI): 0.44 (0.31–0.62)). Additionally, the nonlinear dose–response associations between progesterone and pregnenolone with prediabetes and T2DM were found. Interactive effects of progesterone and pregnenolone on prediabetes and T2DM were observed, and these significant associations remained in gender-stratified analysis. Conclusions Prediabetes and T2DM were positively linked to serum concentration of progesterone and negatively related to pregnenolone in a dose–response manner in Chinese rural population.

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5

Legacki, Erin L., Barry A. Ball, C. Jo Corbin, Shavahn C. Loux, Kirsten E. Scoggin, Scott D. Stanley, and Alan J. Conley. "Equine fetal adrenal, gonadal and placental steroidogenesis." Reproduction 154, no. 4 (October 2017): 445–54. http://dx.doi.org/10.1530/rep-17-0239.

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Equine fetuses have substantial circulating pregnenolone concentrations and thus have been postulated to provide significant substrate for placental 5α-reduced pregnane production, but the fetal site of pregnenolone synthesis remains unclear. The current studies investigated steroid concentrations in blood, adrenal glands, gonads and placenta from fetuses (4, 6, 9 and 10 months of gestational age (GA)), as well as tissue steroidogenic enzyme transcript levels. Pregnenolone and dehydroepiandrosterone (DHEA) were the most abundant steroids in fetal blood, pregnenolone was consistently higher but decreased progressively with GA. Tissue steroid concentrations generally paralleled those in serum with time. Adrenal and gonadal tissue pregnenolone concentrations were similar and 100-fold higher than those in allantochorion. DHEA was far higher in gonads than adrenals and progesterone was higher in adrenals than gonads. Androstenedione decreased with GA in adrenals but not in gonads. Transcript analysis generally supported these data.CYP17A1was higher in fetal gonads than adrenals or allantochorion, andHSD3B1was higher in fetal adrenals and allantochorion than gonads.CYP11A1transcript was also significantly higher in adrenals and gonads than allantochorion andCYP19and SRD5A1 transcripts were higher in allantochorion than either fetal adrenals or gonads. Given these data, and their much greater size, the fetal gonads are the source of DHEA and likely contribute more than fetal adrenal glands to circulating fetal pregnenolone concentrations. LowCYP11A1but highHSD3B1andSRD5A1transcript abundance in allantochorion, and low tissue pregnenolone, suggests that endogenous placental pregnenolone synthesis is low and likely contributes little to equine placental 5α-reduced pregnane secretion.

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6

Costa, Barbara, Stefano Pini, Pamela Gabelloni, Eleonora Da Pozzo, Marianna Abelli, Lisa Lari, Matteo Preve, Antonio Lucacchini, Giovanni B. Cassano, and Claudia Martini. "The Spontaneous Ala147Thr Amino Acid Substitution within the Translocator Protein Influences Pregnenolone Production in Lymphomonocytes of Healthy Individuals." Endocrinology 150, no. 12 (October 21, 2009): 5438–45. http://dx.doi.org/10.1210/en.2009-0752.

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Abstract The de novo production of steroids and neurosteroids begins in mitochondria by the conversion of cholesterol to pregnenolone through cytochrome P450 side-chain cleavage (CYP11A1) enzymatic activity. The C-terminal amino acid domain of the translocator protein (TSPO) has been demonstrated to bind cholesterol, thereby determining its mitochondrial translocation. The goal of the present study was to investigate the effect of the Ala147Thr single-nucleotide polymorphism localized in this TSPO region on pregnenolone production in healthy volunteers. Pregnenolone production was evaluated in a peripheral cell model, represented by circulating lymphomonocytes. First, CYP11A1 expression, both at mRNA and protein level, was demonstrated. Pregnenolone production varied among genotype groups. Comparison of pregnenolone mean values revealed that Thr147 homozygous or heterozygous individuals had significantly lower pregnenolone levels compared with Ala147 homozygous individuals. These findings suggested a dominant effect of the minor allelic variant Thr147 to produce this first metabolite of the steroidogenesis pathway. Interestingly, Ala147 homozygous individuals exhibited significant higher levels of circulating cholesterol-rich low-density lipoproteins with respect to heterozygous individuals. In conclusion, our results demonstrate that the Ala147Thr spontaneous amino acid substitution within TSPO is able to affect pregnenolone production; this should encourage further studies to investigate its potential role in polygenic dyslipidemias.

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7

Vallée, Monique, Sergio Vitiello, Luigi Bellocchio, Etienne Hébert-Chatelain, Stéphanie Monlezun, Elena Martin-Garcia, Fernando Kasanetz, et al. "Pregnenolone Can Protect the Brain from Cannabis Intoxication." Science 343, no. 6166 (January 2, 2014): 94–98. http://dx.doi.org/10.1126/science.1243985.

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Pregnenolone is considered the inactive precursor of all steroid hormones, and its potential functional effects have been largely uninvestigated. The administration of the main active principle of Cannabis sativa (marijuana), ∆9-tetrahydrocannabinol (THC), substantially increases the synthesis of pregnenolone in the brain via activation of the type-1 cannabinoid (CB1) receptor. Pregnenolone then, acting as a signaling-specific inhibitor of the CB1 receptor, reduces several effects of THC. This negative feedback mediated by pregnenolone reveals a previously unknown paracrine/autocrine loop protecting the brain from CB1 receptor overactivation that could open an unforeseen approach for the treatment of cannabis intoxication and addiction.

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8

French, Joseph T., and Thomas H. Welsh. "In vitro modulation of porcine Leydig cell steroidogenesis by phorbol-12-myristate-13-acetate and 1,2-dioctanoylglycerol." Acta Endocrinologica 122, no. 1 (January 1990): 101–6. http://dx.doi.org/10.1530/acta.0.1220101.

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Abstract Serum-free primary cultures of neonatal (1-day-old) porcine Leydig cells were used to study the effects of phorbol-12-myristate-13-acetate and 1,2-dioctanoylglycerol on testosterone and pregnenolone production. Phorbol-12-myristate-13-acetate alone from 0.001-10 μmol/l stimulated testosterone and pregnenolone production, whereas 1,2-dioctanoylglycerol alone had no effect on steroid production, relative to control. Phorbol12-myristate-13-acetate and 1,2-dioctanoylglycerol each inhibited pLH-stimulated testosterone and pregnenolone production. To further clarify the influence of these protein kinase C activators on steroidogenesis, cultured Leydig cells were treated with either phorbol-12-myristate-13-acetate or 1,2-dioctanoylglycerol plus forskolin (an adenylate cyclase activator). Both phorbol-12-myristate-13-acetate and 1,2-dioctanoylglycerol inhibited forskolin-stimulated testosterone production. Phorbol-12-myristate-13-acetate had no effect on forskolin-stimulated pregnenolone production and only the highest concentration of 1,2-dioctanoylglycerol (100 μmol/l) inhibited forskolin-stimulated production of pregnenolone. These data demonstrate that porcine Leydig cell steroidogenesis can be modulated by interactions of the protein kinase C and protein kinase A second messenger systems.

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9

Mayer, Sabine I., Isabelle Müller, Stefanie Mannebach, Takeshi Endo, and Gerald Thiel. "Signal Transduction of Pregnenolone Sulfate in Insulinoma Cells." Journal of Biological Chemistry 286, no. 12 (January 21, 2011): 10084–96. http://dx.doi.org/10.1074/jbc.m110.202697.

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The neurosteroid pregnenolone sulfate acts on the nervous system by modifying neurotransmission and receptor functions, thus influencing synaptic strength, neuronal survival, and neurogenesis. Here we show that pregnenolone sulfate induces a signaling cascade in insulinoma cells leading to enhanced expression of the zinc finger transcription factor Egr-1 and Egr-1-responsive target genes. Pharmacological and genetic experiments revealed that influx of Ca2+ ions via transient receptor potential M3 and voltage-gated Ca2+ channels, elevation of the cytosolic Ca2+ level, and activation of ERK are essential for connecting pregnenolone sulfate stimulation with enhanced Egr-1 biosynthesis. Expression of a dominant-negative mutant of Elk-1, a key regulator of gene transcription driven by a serum response element, attenuated Egr-1 expression following stimulation, indicating that Elk-1 or related ternary complex factors connect the transcription of the Egr-1 gene with the pregnenolone sulfate-induced intracellular signaling cascade elicited by the initial influx of Ca2+. The newly synthesized Egr-1 was biologically active and bound under physiological conditions to the regulatory regions of the Pdx-1, Synapsin I, and Chromogranin B genes. Pdx-1 is a major regulator of insulin gene transcription. Accordingly, elevated insulin promoter activity and increased mRNA levels of insulin could be detected in pregnenolone sulfate-stimulated insulinoma cells. Likewise, the biosynthesis of synapsin I, a synaptic vesicle protein that is found at secretory granules in insulinoma cells, was stimulated in pregnenolone sulfate-treated INS-1 cells. Together, these data show that pregnenolone sulfate induces a signaling cascade in insulinoma cells that is very similar to the signaling cascade induced by glucose in β-cells.

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10

Lambert, F., J. Lammerant, and J. Kolanowski. "The mechanism of the prolonged stimulatory effect of corticotrophin on pregnenolone production by guinea-pig adrenocortical mitochondria." Journal of Endocrinology 108, no. 3 (March 1986): 377–84. http://dx.doi.org/10.1677/joe.0.1080377.

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ABSTRACT The postulated prolonged stimulatory influence of ACTH on the adrenocortical mitochondrial synthesis of pregnenolone in response to ACTH was studied in adrenal mitochondria isolated from control guinea-pigs and from animals treated s.c. with 100 μg ACTH(1–24) twice daily on the day before the animals were killed. The animals from both groups were injected with 100 μg ACTH s.c. 30 min before killing. The mitochondrial production of pregnenolone (expressed in nmol per mg mitochondrial protein after 10-min incubation) increased from 1·52 ± 0·46 (s.e.m.) in the control group to 4·50 ± 0·59 for mitochondria from ACTH-treated animals, despite a similar free cholesterol content in the mitochondria, even when determined after a previous in-vivo treatment with aminoglutethimide to block further metabolism of cholesterol into pregnenolone. In addition, in the presence of an excess of exogenous cholesterol (100 μmol/l), the production of pregnenolone remained higher for mitochondria from ACTH-treated animals. In contrast, when the calcium concentration in the incubation medium was raised to 1 mmol/l, with subsequent enhancement in pregnenolone synthesis, the mitochondrial pregnenolone production became similar for both groups (8·28 ± 1·11 nmol in the ACTH-treated group and 9·55 ± 1·90 nmol in the control group), even in the presence of 100 μmol cholesterol/l (13·5 ±1·80 nmol in ACTH-treated animals and 14·8 ± 1·93 nmol in controls). Cycloheximide treatment administered on the day before the animals were killed was without any effect on pregnenolone production in control animals (3·51 ± 0·43 nmol before and 3·65 ± 0·63 nmol after cycloheximide treatment). In contrast, the pregnenolone production by mitochondria from ACTH-treated guinea-pigs injected with cycloheximide was reduced to a level similar to that observed in the control group (5·82± 0·23 nmol in the absence and 3·09± 0·32nmol in the presence of cycloheximide treatment). The results of the present study suggest that the prolonged stimulatory effect of ACTH on pregnenolone production involves an increase in the synthesis of a protein factor which promotes the availability of cholesterol to the side-chain cleavage system. Other mechanisms such as a stimulated synthesis of the side-chain cleavage complex itself or an increased total mitochondrial cholesterol content are not supported by our data. J. Endocr. (1986) 108, 377–384

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11

Badran, Serene Adnan, Atia-tul-Wahab, Sharmeen Fayyaz, Bushra Taj Muhammad, and Muhammad Iqbal Choudhary. "Effect of Steroidal Hormone Pregnenolone on Proliferation and Differentiation of MC3T3-E1 Osteoblast like Cells." Letters in Drug Design & Discovery 17, no. 9 (September 11, 2020): 1139–45. http://dx.doi.org/10.2174/1570180817666200204110859.

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Background: Bone remodeling is a complex process that includes continuous resorption by osteoclast cells and bone formation by osteoblast cells. Bone fragility is a common health issue of the elderly population, particularly in postmenopausal women. It has been established that steroidal hormones have an important role in bone homeostasis. Therefore hormone replacement therapy could have beneficial effects on bone health as compared to other treatments. Objectives: An imbalance between the rate of bone formation and bone resorption leads to the fragility of bones. During the current study, we aimed to explore the ability of pregnenolone (1) (PRE), on proliferation and differentiation of MC3T3-E1 cells. We further aimed to investigate the underlying mechanism of action for the anabolic effect of PRE (1). Methods: The effects of pregnenolone (1) on proliferation, differentiation, and mineralization of MC3T3 osteoblast-like cells were determined. Cell viability was analyzed using MTT assay and flow cytometry. ALP activity and alizarin staining were employed to evaluate the effect of pregnenolone on osteoblast differentiation. Moreover, western blot for analysis of certain important proteins, crucial for the regulation of bone homeostasis, such as BMP2 and RANKL, was also performed. Results: Our results showed that pregnenolone (1) at a concentration of 5 μM caused a significant (p< 0.05) rise in the growth of MC3T3-E1 cells, whereas a comparable effect was observed in osteoblast differentiating assays. A significant decrease in RANKL expression was observed at (0.04 – 1 .M). Our results, therefore, indicated the possible role of pregnenolone (1) in positive regulation of bone homeostasis by suppressing RANKL expression. Conclusion: Taken together, our results indicate that pregnenolone (1) has the potential to enhance osteoblast proliferation, as inferred from the increased number of cells. These results demonstrated that pregnenolone (1) could be a potential anabolic agent for the treatment of fragility related disorders.

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12

Stone, BA, RF Seamark, RW Kelly, and S. Deam. "Production of Steroids and Release of Prostaglandins by Spherical Pig Blastocysts in vitro." Australian Journal of Biological Sciences 39, no. 3 (1986): 283. http://dx.doi.org/10.1071/bi9860283.

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Levels of pregnenolone and progesterone in spherical pig blastocysts (near 4 and 15 /lM respectively) exceeded respective levels in histotroph by about 400-fold. When blastocysts were cultured for 5 days in a synthetic medium containing pregnenolone sulfate (l /lM), daily rates of release of pregnenolone, progesterone, androstenedione, testosterone, oestrone and oestradiol were determined to be near 320, 45, 2.6, 27, O' 8 and 9� 2 fmol per blastocyst respectively. Daily outputs of progesterone and testosterone (fmol per blastocyst) diminished (P < O' 05) to l' 3 and undetectable levels � 2) respectively in the presence of Trilostane (94 /lM). Increasing the content of pregnenolone sulfate in the culture medium (to 4�5 /lM) resulted in higher daily rates of release of pregnenolone and progesterone (to near 1740 and 380 fmol per blastocyst respectively), verifying activity of 3i1-hydroxy-Ll5-steroid dehydrogenase, and of arylsulfatase, in tissues of intact spherical pig blastocysts. Prostaglandin E2 was the predominant prostaglandin (PG) released by cultured blastocysts (about 1 fmol per blastocyst per hour), hourly rates of release of PGH2 (derived) and PGF2" being near 0�1 and <0�06 fmol per blastocyst respectively.

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13

Lone, Imtiyaz H., and M. Amin Bhat. "Synthesis, Molecular Properties and MIC Studies of D-Ring Chalcone Derivatives of 20-Keto Pregnenolone." Materials Science Forum 760 (July 2013): 15–22. http://dx.doi.org/10.4028/www.scientific.net/msf.760.15.

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An efficient and simple synthesis of 17-chalconyl derivatives of pregnenolone and their antibacterial and antifungal evaluation is reported. The scheme involves the transformation of the starting pregnenolone to the corresponding Chalcone derivatives by the well-known Claisen-Schmidt reaction. Determination of Minimum inhibitory concentrations (MICs) is reported on these newly synthesized Chalcone derivatives of pregnenolone. The prediction of molecular properties is also discussed. Compounds showing lower MIC values also followedLipinski’s rule of 5. The results showed that the activity of the tested agents against each microbe varies due to structural differences between the microorganisms.

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14

Naylor, Jennifer C., Christine M. Hulette, David C. Steffens, Lawrence J. Shampine, John F. Ervin, Victoria M. Payne, Mark W. Massing, et al. "Cerebrospinal Fluid Dehydroepiandrosterone Levels Are Correlated with Brain Dehydroepiandrosterone Levels, Elevated in Alzheimer’s Disease, and Related to Neuropathological Disease Stage." Journal of Clinical Endocrinology & Metabolism 93, no. 8 (August 1, 2008): 3173–78. http://dx.doi.org/10.1210/jc.2007-1229.

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Abstract Objective: It is currently unknown whether cerebrospinal fluid (CSF) neurosteroid levels are related to brain neurosteroid levels in humans. CSF and brain dehydroepiandrosterone (DHEA) levels are elevated in patients with Alzheimer’s disease (AD), but it is unclear whether CSF DHEA levels are correlated with brain DHEA levels within the same subject cohort. We therefore determined DHEA and pregnenolone levels in AD patients (n = 25) and cognitively intact control subjects (n = 16) in both CSF and temporal cortex. Design: DHEA and pregnenolone levels were determined by gas chromatography/mass spectrometry preceded by HPLC. Frozen CSF and temporal cortex specimens were provided by the Alzheimer’s Disease Research Center at Duke University Medical Center. Data were analyzed by Mann-Whitney U test statistic and Spearman correlational analyses. Results: CSF DHEA levels are positively correlated with temporal cortex DHEA levels (r = 0.59, P < 0.0001) and neuropathological disease stage (Braak and Braak) (r = 0.42, P = 0.007). CSF pregnenolone levels are also positively correlated with temporal cortex pregnenolone levels (r = 0.57, P < 0.0001) and tend to be correlated with neuropathological disease stage (Braak) (r = 0.30, P = 0.06). CSF DHEA levels are elevated (P = 0.032), and pregnenolone levels tend to be elevated (P = 0.10) in patients with AD, compared with cognitively intact control subjects. Conclusions: These findings indicate that CSF DHEA and pregnenolone levels are correlated with temporal cortex brain levels of these neurosteroids and that CSF DHEA is elevated in AD and related to neuropathological disease stage. Neurosteroids may thus be relevant to the pathophysiology of AD.

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15

Welberg, Leonie. "Pregnenolone limits effects of cannabis." Nature Reviews Neuroscience 15, no. 2 (January 17, 2014): 66–67. http://dx.doi.org/10.1038/nrn3681.

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16

Prasad, V. V. Kris, and Steven O. Franklin. "Synthesis of (21-3H3)-pregnenolone." Journal of Labelled Compounds and Radiopharmaceuticals 22, no. 4 (April 1985): 353–58. http://dx.doi.org/10.1002/jlcr.2580220407.

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17

Choudhary, Muhammad Iqbal, Iffat Batool, Syed Adnan Ali Shah, Sarfraz Ahmad Nawaz, and Atta-ur-Rahman. "Microbial Hydroxylation of Pregnenolone Derivatives." CHEMICAL & PHARMACEUTICAL BULLETIN 53, no. 11 (2005): 1455–59. http://dx.doi.org/10.1248/cpb.53.1455.

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18

Cheney, D. L., D. Uzunov, and A. Guidotti. "Pregnenolone sulfate antagonizes dizocilpine amnesia." NeuroReport 6, no. 12 (August 1995): 1697–700. http://dx.doi.org/10.1097/00001756-199508000-00025.

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19

Caballero, Gerardo M., and Eduardo G. Gros. "Synthesis of [20,21-13C2]-pregnenolone." Journal of Labelled Compounds and Radiopharmaceuticals 33, no. 10 (October 1993): 907–11. http://dx.doi.org/10.1002/jlcr.2580331004.

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20

Wang, Ming-De, Göran Wahlström, and Torbjörn Bäckström. "The regional brain distribution of the neurosteroids pregnenolone and pregnenolone sulfate following intravenous infusion." Journal of Steroid Biochemistry and Molecular Biology 62, no. 4 (July 1997): 299–306. http://dx.doi.org/10.1016/s0960-0760(97)00041-1.

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21

Melchior, C. L., and R. F. Ritzmann. "Pregnenolone and pregnenolone sulfate, alone and with ethanol, in mice on the plus-maze." Pharmacology Biochemistry and Behavior 48, no. 4 (August 1994): 893–97. http://dx.doi.org/10.1016/0091-3057(94)90197-x.

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22

Netchitailo, P., A. Larcher, F. Leboulenger, M. Feuilloley, D. Philibert, and H. Vaudry. "Self-inhibition of steroid secretion by amphibian adrenocortical cells is not mediated through glucocorticoid receptors." Journal of Molecular Endocrinology 6, no. 3 (June 1991): 249–55. http://dx.doi.org/10.1677/jme.0.0060249.

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ABSTRACT To investigate a possible direct action of glucocorticoids on adrenal steroidogenesis, the effect of corticosterone on the conversion of pregnenolone into various metabolites by frog adrenal tissue was examined. Frog interrenal slices were incubated with [3H]pregnenolone (1 mCi/ml) and the various labelled metabolites analysed by reverse-phase high-performance liquid chromatography. With the methanol gradient used, five identified steroids were resolved: progesterone, 11-deoxycorticosterone, corticosterone, 18-hydroxycorticosterone and aldosterone. Corticosterone (10 μg/ml) induced a 45–80% decrease in all steroids synthesized from [3H]pregnenolone. In contrast, the glucocorticoid agonist dexamethasone did not reduce the rate of conversion of pregnenolone into its metabolites. In addition, the inhibitory effect of corticosterone was not reversed by the specific glucocorticoid antagonist RU 43044. These results show that corticosterone exerts a direct inhibitory effect on adrenal steroid secretion. In addition, our data indicate that the ultra-short regulation induced by corticosterone is not mediated through glucocorticoid receptors.

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23

Shumyantseva, V. V., T. V. Bulko, A. Yu Misharin, and A. I. Archakov. "Screening of potential substrates or inhibitors of cytochrome P450 17a1 (CYP17a1) by electrochemical methods." Biomeditsinskaya Khimiya 57, no. 4 (2011): 402–9. http://dx.doi.org/10.18097/pbmc20115704402.

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The electrochemical reduction of the recombinant form of human cytochrome P450 17A1 (CYP17A1) was investigated. Hemeprotein was immobilized on electrode modified with biocompatable nanocomposite material based on the membrane-like synthetic surfactant didodecyldimethylammonium bromide (DDAB) and gold nanoparticles. Analytical characteristics of DDAB/Au/CYP17A1 electrodes were investigated with cyclic voltammetry, square wave voltammetry, and differential pulse voltammetry. Analysis of electrochemical behaviour of cytochrome P450 17A1 was conducted in the presence of substrate pregnenolone (1), inhibitor ketoconazole (2), and in the presence of synthetic derivatives of pregnenolone: acetylpregnenolone (3), cyclopregnenolone (4), and tetrabrompregnenolone (5). Ketoconazole, azole inhibitor of cytochromes P450, blocked catalytic current in the presence of substrate pregnenolone (1). Compounds 3-5 did not demonstrate substrate properties towards electrode/CYP17A1 system. Compound 3 did not block catalytic activity towards pregnenolone, but compounds 4 and 5 inhibited such activity. Electrochemical reduction of CYP17A1 may serve as an adequate substitution of the reconstituted system which requires additional redox partners - for the exhibition of catalytic activity of hemoproteins of the cytochrome P450 superfamily.

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Havlíková, Helena, Martin Hill, Richard Hampl, and Luboš Stárka. "Sex- and Age-Related Changes in Epitestosterone in Relation to Pregnenolone Sulfate and Testosterone in Normal Subjects." Journal of Clinical Endocrinology & Metabolism 87, no. 5 (May 1, 2002): 2225–31. http://dx.doi.org/10.1210/jcem.87.5.8499.

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Epitestosterone has been demonstrated to act at various levels as a weak antiandrogen. So far, its serum levels have been followed up only in males. Epitestosterone and its major circulating precursor pregnenolone sulfate and T were measured in serum from 211 healthy women and 386 men to find out whether serum concentrations of epitestosterone are sufficient to exert its antiandrogenic actions. In women, epitestosterone exhibited a maximum around 20 yr of age, followed by a continuous decline up to menopause and by a further increase in the postmenopause. In men, maximum epitestosterone levels were detected at around 35 yr of age, followed by a continuous decrease. Pregnenolone sulfate levels in women reached their maximum at about age 32 yr and then declined continuously, and in males the maximum was reached about 5 yr earlier and then remained nearly constant. Epitestosterone correlated with pregnenolone sulfate only in males. In both sexes a sharp decrease of the epitestosterone/T ratio around puberty occurred. In conclusion, concentrations of epitestosterone and pregnenolone sulfate are age dependent and, at least in prepubertal boys and girls, epitestosterone reaches or even exceeds the concentrations of T, thus supporting its role as an endogenous antiandrogen. The dissimilarities in the course of epitestosterone levels through the lifespan of men and women and its relation to pregnenolone sulfate concentrations raise the question of the contribution of the adrenals and gonads to the production of both steroids and even to the uniformity of the mechanism of epitestosterone formation.

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Deb, Subrata, Steven Pham, Dong-Sheng Ming, Mei Chin, Hans Adomat, Antonio Hurtado-Coll, Martin Gleave, and Emma Guns. "Characterization of Precursor-Dependent Steroidogenesis in Human Prostate Cancer Models." Cancers 10, no. 10 (September 20, 2018): 343. http://dx.doi.org/10.3390/cancers10100343.

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Castration-resistant prostate tumors acquire the independent capacity to generate androgens by upregulating steroidogenic enzymes or using steroid precursors produced by the adrenal glands for continued growth and sustainability. The formation of steroids was measured by liquid chromatography-mass spectrometry in LNCaP and 22Rv1 prostate cancer cells, and in human prostate tissues, following incubation with steroid precursors (22-OH-cholesterol, pregnenolone, 17-OH-pregnenolone, progesterone, 17-OH-progesterone). Pregnenolone, progesterone, 17-OH-pregnenolone, and 17-OH-progesterone increased C21 steroid (5-pregnan-3,20-dione, 5-pregnan-3,17-diol-20-one, 5-pregnan-3-ol-20-one) formation in the backdoor pathway, and demonstrated a trend of stimulating dihydroepiandrosterone or its precursors in the backdoor pathway in LNCaP and 22Rv1 cells. The precursors differentially affected steroidogenic enzyme messenger RNA (mRNA) expressions in the cell lines. The steroidogenesis following incubation of human prostate tissue with 17-OH-pregnenolone and progesterone produced trends similar to those observed in cell lines. Interestingly, the formation of C21 steroids from classical pathway was not stimulated but backdoor pathway steroids (e.g., 5-pregnan-3,20-dione, 5-pregnan-3-ol-20-one) were elevated following incubations with prostate tissues. Overall, C21 steroids were predominantly formed in the classical as well as backdoor pathways, and steroid precursors induced a diversion of steroidogenesis to the backdoor pathway in both cell lines and human prostate tissue, and influenced adaptive steroidogenesis to form C21 steroids.

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26

Banday, Abid H., Shameem A. Shameem, Javid A. Banday, and Bashir A. Ganaie. "Synthesis, 17α-hydroxylase-C17,20-lyase Inhibitory and 5AR Reductase Activity of Novel Pregnenolone Derivatives." Anti-Cancer Agents in Medicinal Chemistry 18, no. 13 (February 14, 2019): 1919–26. http://dx.doi.org/10.2174/1871520618666180426100942.

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Background: The potential of steroids for development into lead pharmacological molecules lies in the regulation of a variety of biological processes by these molecules and also because of these being a fundamental class of signaling molecules. Steroid based scaffolds have been extensively used as active pharmaceutical agents for the treatment of various diseases including the deadly disease of cancer which despite the recent advances in the early diagnosis, prevention and therapy, remains a clinical challenge affecting millions of people world over and is one of the leading causes of death. It thus warrants the development of new drugs against this dreadful disease through exploitation of emerging molecularly defined targets. Methods: The present study explores the effect of novel steroidal pyrazolines as presumed inhibitors of 5α- reductase (5AR) and 17α-hydroxylase-C17,20-lyase as a target for treatment of prostate cancer. A series of 1,5- diaryl pyrazoline pregnenolones were synthesized and screened for 5α-reductase inhibitory activities. Synthesis of the analogs is multistep and proceeds in good overall yields. The key step in the synthesis of 1,5- disubstituted pyrazolinyl pregnenolones is the heterocyclization of bezylidine derivatives (3) in presence of phenylhydrazines (4) through the initial formation of the phenylhydrazones, which undergo concomitant cyclization to generate the stable pyrazoline derivatives. Results: All the synthesised D-ring 1,5-disubstituted pyrazolinyl pregnenolone derivatives (5a-l) were screened for prostate cancer cell inhibitory, 5α-reductase and 17α-hydroxylase-C17,20-lyase inhibitory activity. Amongst all the compounds screened for their 5α-reductase inhibitory activities, compound 5c, 5e, 5g and 5l were found to be the most active. Further, compounds 5g and 5h were found to have moderate 17α-hydroxylase-C17,20-lyase inhibitory activities. Conclusion: A series of D-ring 1,5-disubstituted pyrazolinyl pregnenolone derivatives (5a-l) were synthesized and screened for their prostate cancer cell inhibitory, 5a-reductase and 17α-hydroxylase-C17,20-lyase inhibitory activity. Amongst all the compounds screened for their 5α-reductase inhibitory activities, compound 5c, 5e, 5g and 5l were found to be the most active whereas compounds 5g and 5h were found to have moderate 17α- hydroxylase-C17,20-lyase inhibitory activities.

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Panada, J. U., Y. V. Faletrov, N. S. Frolova, and V. M. Shkumatov. "Synthesis and evaluation of N-alkynylaminosteroids as potential CYP450 17A1 inhibitors." Biomeditsinskaya Khimiya 65, no. 4 (2019): 324–30. http://dx.doi.org/10.18097/pbmc20196504324.

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Four isomeric dehydroepiandrosterone- and pregnenolone-based N-alkynylaminosteroids were synthesized and tested in vitro for inhibition of heterologously expressed CYP17A1. The highest inhibitory activity was observed when the optimal number of side chain atoms was met. The conjugate based on pregnenolone containing an N-propynyl moiety was found to interefere with enzymatic activity most effectively and consistently in the micromolar range.

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28

Mannowetz, Nadja, Melissa R. Miller, and Polina V. Lishko. "Regulation of the sperm calcium channel CatSper by endogenous steroids and plant triterpenoids." Proceedings of the National Academy of Sciences 114, no. 22 (May 15, 2017): 5743–48. http://dx.doi.org/10.1073/pnas.1700367114.

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The calcium channel of sperm (CatSper) is essential for sperm hyperactivated motility and fertility. The steroid hormone progesterone activates CatSper of human sperm via binding to the serine hydrolase ABHD2. However, steroid specificity of ABHD2 has not been evaluated. Here, we explored whether steroid hormones to which human spermatozoa are exposed in the male and female genital tract influence CatSper activation via modulation of ABHD2. The results show that testosterone, estrogen, and hydrocortisone did not alter basal CatSper currents, whereas the neurosteroid pregnenolone sulfate exerted similar effects as progesterone, likely binding to the same site. However, physiological concentrations of testosterone and hydrocortisone inhibited CatSper activation by progesterone. Additionally, testosterone antagonized the effect of pregnenolone sulfate. We have also explored whether steroid-like molecules, such as the plant triterpenoids pristimerin and lupeol, affect sperm fertility. Interestingly, both compounds competed with progesterone and pregnenolone sulfate and significantly reduced CatSper activation by either steroid. Furthermore, pristimerin and lupeol considerably diminished hyperactivation of capacitated spermatozoa. These results indicate that (i) pregnenolone sulfate together with progesterone are the main steroids that activate CatSper and (ii) pristimerin and lupeol can act as contraceptive compounds by averting sperm hyperactivation, thus preventing fertilization.

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29

Yildirim, Kudret, Ahmet Uzuner, and Emine Yasemin Gulcuoglu. "Biotransformation of some steroids by Aspergillus terreus MRC 200365." Collection of Czechoslovak Chemical Communications 75, no. 6 (2010): 665–73. http://dx.doi.org/10.1135/cccc2009545.

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The biotransformations of testosterone, epiandrosterone, progesterone and pregnenolone byAspergillus terreusMRC 200365 for five days were described. The biotransformation of testosterone afforded testolactone. The biotransformation of epiandrosterone afforded 3β-hydroxy-17a-oxa-D-homo-5α-androstan-17-one. The biotransformation of progesterone afforded androst-4-ene-3,17-dione and testolactone. The biotransformation of pregnenolone afforded 3β-hydroxy-17a-oxa-D-homoandrost-5-en-17-one and testolactone.

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30

Bernès, Sylvain, Hugo Torrens, Angela López-Giral, and Alfredo Buttenklepper. "Pregnenolone hemisuccinate: aP1 structure withZ′ = 4." Acta Crystallographica Section E Structure Reports Online 59, no. 9 (August 23, 2003): o1372—o1375. http://dx.doi.org/10.1107/s160053680301835x.

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31

SAUDAN, C., A. DESMARCHELIER, P. SOTTAS, P. MANGIN, and M. SAUGY. "Urinary marker of oral pregnenolone administration." Steroids 70, no. 3 (March 2005): 179–83. http://dx.doi.org/10.1016/j.steroids.2004.12.007.

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32

Iqbal Choudhary, M., M. Shahab Alam, Atta-ur-Rahman, Sammer Yousuf, Yang-Chang Wu, An-Shen Lin, and F. Shaheen. "Pregnenolone derivatives as potential anticancer agents." Steroids 76, no. 14 (December 2011): 1554–59. http://dx.doi.org/10.1016/j.steroids.2011.09.006.

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33

Morfin, R., J. Young, C. Corpechot, B. Egestad, J. Sjovall, and E. E. Baulieu. "Neurosteroids: pregnenolone in human sciatic nerves." Proceedings of the National Academy of Sciences 89, no. 15 (August 1, 1992): 6790–93. http://dx.doi.org/10.1073/pnas.89.15.6790.

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34

Hanson, James R., and Kudret Yildirim. "Steroidal Aphidicolin Analogues Derived from Pregnenolone." Journal of Chemical Research, no. 12 (1999): 698–99. http://dx.doi.org/10.1039/a905656d.

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35

Majewska, Maria Dorota, Marie-Therese Bluet-Pajot, Paul Robel, and Etienne-Emile Baulieu. "Pregnenolone sulfate antagonizes barbiturate-induced hypnosis." Pharmacology Biochemistry and Behavior 33, no. 3 (July 1989): 701–3. http://dx.doi.org/10.1016/0091-3057(89)90410-3.

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36

Hanson, James R., and Kudret Yildirim. "Steroidal Aphidicolin Analogues Derived from Pregnenolone." Journal of Chemical Research 23, no. 12 (December 1999): 698–99. http://dx.doi.org/10.1177/174751989902301207.

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The conversion of pregnenolone into the 3β,5α-, 3α,5α-, 4β,5α-, 3α,4α-, 3α,4β- and 3α,4α-dihydroxy derivatives of 17β-hydroxymethyl-5β-androstane as steroidal analogues of the diterpenoid DNA polymerase α inhibitor, aphidicolin, is described.

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37

Yu, Frank H., Young W. Yun, Basil Ho Yuen, and Young S. Moon. "Effects of hydroxyflutamide on rats treated with a superovulatory dose of pregnant mare serum gonadotropin." Canadian Journal of Physiology and Pharmacology 69, no. 2 (February 1, 1991): 185–90. http://dx.doi.org/10.1139/y91-027.

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Immature female rats treated with superovulatory doses of pregnant mare serum gonadotropin (PMSG) were used to study the effects of the antiandrogen hydroxyflutamide on steroid production, particularly the biologically active androgens, in two experiments. In the first experiment, animals were given either 5 mg hydroxyflutamide or vehicle alone at 30 and 36 h following 40 IU PMSG. Compared with the vehicle group, hydroxyflutamide treatment significantly reduced the percentage of degenerate oocytes recovered from oviducts (p < 0.05). Serum levels of testosterone and androstenedione, and their aromatized product 17β-estradiol, significantly decreased (p < 0.05) in the hydroxyflutamide-treated group; however, nonaromatizable androgen, 5α-dihydrotestosterone, was not affected. In the second experiment, ovaries obtained 48 h after stimulation with 4 or 40 IU PMSG were incubated with and without hydroxyflutamide (10−5 M) and (or) testosterone (10−7 M) to study [4-14C]pregnenolone metabolism to major steroids. In 40 IU stimulated ovaries, hydroxyflutamide significantly decreased the metabolism of pregnenolone to progesterone (p < 0.01) and androstenedione (p < 0.01), while the production of 17β-estradiol increased significantly (p < 0.05); however, pregnenolone conversions to testosterone and 5α-dihydrotestosterone were not affected. Testosterone completely reversed the hydroxyflutamide-induced alteration of pregnenolone metabolism. In contrast, there was no difference in the pregnenolone conversion patterns between untreated and hydroxyflutamide or hydroxyflutamide plus testosterone groups in 4 IU stimulated ovaries. Present results confirm our previous finding that hydroxyflutamide decreases the percentage of abnormal oocytes recovered from superovulating rats and indicates that this hydroxyflutamide effect may be partly mediated by altered ovarian steroidogenesis following inhibition of androgen binding in the ovary.Key words: superovulation, pregnant mare serum gonadotropin, antiandrogen, hydroxyflutamide, androgen.

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38

Yildirim, Kudret. "Microbial hydroxylation of some steroids by Aspergillus wentii MRC 200316." Collection of Czechoslovak Chemical Communications 75, no. 12 (2010): 1273–81. http://dx.doi.org/10.1135/cccc2010112.

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Biotransformations of epiandrosterone (1), dehydroepiandrosterone (2) and pregnenolone (3) byAspergillus wentiiMRC 200316 for 5 days have been reported. Incubation of epiandrosterone (1) afforded 11α-hydroxy-5α-androstane-3,17-dione (4) and 3β,11α-dihydroxy-5α-androstan-17-one (5). Incubation of dehydroepiandrosterone (2) afforded 3β,7β-di-hydroxyandrost-5-en-17-one (6) and 3β,7α-dihydroxyandrost-5-en-17-one (7). Incubation of pregnenolone (3) afforded only 11α-hydroxypregn-4-ene-3,20-dione (8).

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39

Mikami, K., M. Omura, Y. Tamura, and S. Yoshida. "Possible site of action of 5-hydroperoxyeicosatetraenoic acid derived from arachidonic acid in ACTH-stimulated steroidogenesis in rat adrenal glands." Journal of Endocrinology 125, no. 1 (April 1990): 89–96. http://dx.doi.org/10.1677/joe.0.1250089.

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ABSTRACT The site of action of 5-hydroperoxyeicosatetraenoic acid (5-HPETE) in ACTH-induced stimulation of steroidogenesis was examined in rat adrenocortical fasciculata cells. Prior addition of AA861, a specific inhibitor of 5-lipoxygenase, had no significant effect on cyclic AMP-dependent protein kinase activity and cholesterol esterase activities, when stimulated by ACTH in adrenocortical cells, compared with that stimulated by ACTH alone. Cholesterol accumulation in the mitochondria of cells treated with ACTH and cycloheximide was also not altered by pretreatment with AA861. We found, however, that pregnenolone formation, stimulated by ACTH, decreased in a dose-dependent manner when cells were pretreated with AA861. The inhibition of ACTH-stimulated pregnenolone formation by treatment with AA861 was restored only by prior addition of 5-HPETE. Furthermore, addition of AA861 also did not affect the conversion of pregnenolone into corticosterone. In conclusion, 5-HPETE may act at the level of the mitochondria in ACTH-induced steroidogenesis in rat adrenal fasciculata cells. Journal of Endocrinology (1990) 125, 89–96

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40

Witzig, Melissa, Amandine Grimm, Karen Schmitt, Imane Lejri, Stephan Frank, Steven A. Brown, and Anne Eckert. "Clock-Controlled Mitochondrial Dynamics Correlates with Cyclic Pregnenolone Synthesis." Cells 9, no. 10 (October 19, 2020): 2323. http://dx.doi.org/10.3390/cells9102323.

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Neurosteroids are steroids synthetized in the nervous system, with the first step of steroidogenesis taking place within mitochondria with the synthesis of pregnenolone. They exert important brain-specific functions by playing a role in neurotransmission, learning and memory processes, and neuroprotection. Here, we show for the first time that mitochondrial neurosteroidogenesis follows a circadian rhythm and correlates with the rhythmic changes in mitochondrial morphology. We used synchronized human A172 glioma cells, which are steroidogenic cells with a functional core molecular clock, to show that pregnenolone levels and translocator protein (TSPO) are controlled by the clock, probably via circadian regulation of mitochondrial fusion/fission. Key findings were recapitulated in mouse brains. We also showed that genetic or pharmacological abrogation of fusion/fission activity, as well as disturbing the core molecular clock, abolished circadian rhythms of pregnenolone and TSPO. Our findings provide new insights into the crosstalk between mitochondrial function (here, neurosteroidogenesis) and circadian cycles.

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41

Abunnaja, Maryam S., Fatemah A. Alherz, Amal A. El Daibani, Ahsan F. Bairam, Mohammed I. Rasool, Saud A. Gohal, Katsuhisa Kurogi, Masahito Suiko, Yoichi Sakakibara, and Ming-Cheh Liu. "Effects of genetic polymorphisms on the sulfation of dehydroepiandrosterone and pregnenolone by human cytosolic sulfotransferase SULT2A1." Biochemistry and Cell Biology 96, no. 5 (October 2018): 655–62. http://dx.doi.org/10.1139/bcb-2017-0341.

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The cytosolic sulfotransferase (SULT) SULT2A1 is known to mediate the sulfation of DHEA as well as some other hydroxysteroids such as pregnenolone. The present study was designed to investigate how genetic polymorphisms of the human SULT2A1 gene may affect the sulfation of DHEA and pregnenolone. Online databases were systematically searched to identify human SULT2A1 single nucleotide polymorphisms (SNPs). Of the 98 SULT2A1 non-synonymous coding SNPs identified, seven were selected for further investigation. Site-directed mutagenesis was used to generate cDNAs encoding these seven SULT2A1 allozymes, which were expressed in BL21 Escherichia coli cells and purified by glutathione-Sepharose affinity chromatography. Enzymatic assays revealed that purified SULT2A1 allozymes displayed differential sulfating activity toward both DHEA and pregnenolone. Kinetic analyses showed further differential catalytic efficiency and substrate affinity of the SULT2A1 allozymes, in comparison with wild-type SULT2A1. These findings provided useful information concerning the effects of genetic polymorphisms on the sulfating activity of SULT2A1 allozymes.

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42

Vallée, Monique. "Neurosteroids and potential therapeutics: Focus on pregnenolone." Journal of Steroid Biochemistry and Molecular Biology 160 (June 2016): 78–87. http://dx.doi.org/10.1016/j.jsbmb.2015.09.030.

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43

Ford, Sarah L., Adam J. Reinhart, Yevgeniya Lukyanenko, James C. Hutson, and Douglas M. Stocco. "Pregnenolone synthesis in immature rat Sertoli cells." Molecular and Cellular Endocrinology 157, no. 1-2 (November 1999): 87–94. http://dx.doi.org/10.1016/s0303-7207(99)00155-0.

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44

Hu, Z. Y., E. Bourreau, I. Jung-Testas, P. Robel, and E. E. Baulieu. "Neurosteroids: oligodendrocyte mitochondria convert cholesterol to pregnenolone." Proceedings of the National Academy of Sciences 84, no. 23 (December 1, 1987): 8215–19. http://dx.doi.org/10.1073/pnas.84.23.8215.

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45

Rogers, Maximillian A., Jay Liu, Mark M. Kushnir, Elena Bryleva, Alan L. Rockwood, A. Wayne Meikle, David Shapiro, et al. "Cellular Pregnenolone Esterification by Acyl-CoA:Cholesterol Acyltransferase." Journal of Biological Chemistry 287, no. 21 (April 2, 2012): 17483–92. http://dx.doi.org/10.1074/jbc.m111.331306.

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46

Hamasaki, Mayumi, Shigeru Matsumura, Ayaka Satou, Chisato Takahashi, Yukako Oda, Chika Higashiura, Yasushi Ishihama, and Fumiko Toyoshima. "Pregnenolone Functions in Centriole Cohesion during Mitosis." Chemistry & Biology 21, no. 12 (December 2014): 1707–21. http://dx.doi.org/10.1016/j.chembiol.2014.11.005.

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47

Vriens, Joris, Bernd Nilius, and Thomas Voets. "Clotrimazole Potentiates TRPM3 Responses to Pregnenolone Sulfate." Biophysical Journal 98, no. 3 (January 2010): 341a. http://dx.doi.org/10.1016/j.bpj.2009.12.1849.

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48

Cymeryng, CB, LA Dada, and EJ Podesta. "Effect of nitric oxide on rat adrenal zona fasciculata steroidogenesis." Journal of Endocrinology 158, no. 2 (August 1, 1998): 197–203. http://dx.doi.org/10.1677/joe.0.1580197.

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The present study was designed to investigate the role of nitric oxide (NO) in the regulation of adrenocortical function. Different NO donors, such as sodium nitroprusside (SNP), S-nitroso-L-acetyl penicillamine, diethylamine/NO complex sodium salt and diethylenetriamine NO adduct, significantly decreased corticosterone production both in unstimulated and in corticotropin-stimulated zone fasciculata adrenal cells, in a dose-dependent manner. The effect of SNP was reversed by ferrous hemoglobin. A selective inhibitor of NO synthase, L-NG-nitro-arginine significantly increased corticosterone secretion. The effect of SNP was not mediated by cGMP as permeable cGMP analogs did not reproduce its inhibitory effect. SNP significantly inhibited the steroidogenesis stimulated by 8Br-cAMP and 22(R)-OH-cholesterol, but was ineffective when corticosterone was produced in the presence of exogenously added pregnenolone. Moreover, the conversion of [3H]cholesterol to [3H]pregnenolone and the production of pregnenolone or progesterone (assessed by RIA) were significantly decreased by SNP. Taken together, these results suggest that NO may be a negative modulator of adrenal zona fasciculata steroidogenesis.

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49

Rommerts, F. F. G., J. W. Hoogerbrugge, and H. J. van der Molen. "Stimulation of steroid production in isolated rat Leydig cells by unknown factors in testicular fluid differs from the effects of LH or LH-releasing hormone." Journal of Endocrinology 109, no. 1 (April 1986): 111–17. http://dx.doi.org/10.1677/joe.0.1090111.

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ABSTRACT After the addition of charcoal-treated testicular fluid to Leydig cells isolated from 22-day-old rats, pregnenolone production could be increased to a maximum of tenfold within 30 min in a dose-dependent manner. Testicular fluid, but not serum, further increased pregnenolone formation threefold when pregnenolone production by Leydig cells was stimulated by the addition of LH-releasing hormone (fourfold), LH (25-fold) and 22R-hydroxycholesterol (300-fold). The effect of testicular fluid on steroid production in the presence of 22R-hydroxycholesterol was not inhibited by cycloheximide whereas cycloheximide completely inhibited the effect of LH. It appears unlikely that steroids, lipoproteins or other plasma components constitute the stimulatory agents in testicular fluid. The biologically active principles may be locally produced factors with a molecular weight > 25 000. Similar biological activities could be shown in testicular lymph from boars but not in systemic lymph from boars nor in charcoal-treated bovine follicular fluid. The presumably locally produced factor(s) may amplify the effect of LH and can thus act as a local modulator(s). J. Endocr. (1986) 109, 111–117

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50

Chang, Tom, Marc Levine, and Gail D. Bellward. "Influence of sex and inducer treatment on the high- and low-affinity forms of hepatic microsomal erythromycin N-demethylase in rats." Canadian Journal of Physiology and Pharmacology 68, no. 12 (December 1, 1990): 1510–13. http://dx.doi.org/10.1139/y90-229.

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To study the regulation of the multiple forms of erythromycin N-demethylase, we determined the influence of sex and inducer treatment on this mixed-function oxidase activity in adult Wistar rats injected intraperitoneally once daily for 4 days with dexamethasone, pregnenolone-16α-carbonitrile, phenobarbital, or 2% Tween 80 (control). Based on the results from a computer curve-fitting procedure (ENZFITTER) as well as Eadie–Hofstee and Lineweaver–Burk plots, at least two forms of erythromycin N-demethylase were present in control, dexamethasone, pregnenolone-16α-carbonitrile, and phenobarbital-treated male rats and in control and dexamethasone-treated female rats. Only a high-affinity form was apparent in pregneno-lone-16α-carbonitrile and phenobarbital-treated female rats. Therefore, more than one form of erythromycin N-demethylase exists in hepatic microsomes from adult rats, depending on sex and inducer treatment. As well, at a substrate concentration commonly used in the erythromycin N-demethylase assay, the relative contribution of the high- and low-affinity forms to the enzyme activity varies with sex and inducer treatment.Key words: erythromycin N-demethylase, dexamethasone, pregnenolone-16α-carbonitrile, phenobarbital, mixed-function oxidase.

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