Journal articles: 'Steroidogenesis'

1

Baronio, Ortolano, Menabò, Cassio, Baldazzi, Di Natale, Tonti, Vestrucci, and Balsamo. "46,XX DSD due to Androgen Excess in Monogenic Disorders of Steroidogenesis: Genetic, Biochemical, and Clinical Features." International Journal of Molecular Sciences 20, no. 18 (September 17, 2019): 4605. http://dx.doi.org/10.3390/ijms20184605.

Full text

Abstract:

The term ‘differences of sex development’ (DSD) refers to a group of congenital conditions that are associated with atypical development of chromosomal, gonadal, or anatomical sex. Disorders of steroidogenesis comprise autosomal recessive conditions that affect adrenal and gonadal enzymes and are responsible for some conditions of 46,XX DSD where hyperandrogenism interferes with chromosomal and gonadal sex development. Congenital adrenal hyperplasias (CAHs) are disorders of steroidogenesis that mainly involve the adrenals (21-hydroxylase and 11-hydroxylase deficiencies) and sometimes the gonads (3-beta-hydroxysteroidodehydrogenase and P450-oxidoreductase); in contrast, aromatase deficiency mainly involves the steroidogenetic activity of the gonads. This review describes the main genetic, biochemical, and clinical features that apply to the abovementioned conditions. The activities of the steroidogenetic enzymes are modulated by post-translational modifications and cofactors, particularly electron-donating redox partners. The incidences of the rare forms of CAH vary with ethnicity and geography. The elucidation of the precise roles of these enzymes and cofactors has been significantly facilitated by the identification of the genetic bases of rare disorders of steroidogenesis. Understanding steroidogenesis is important to our comprehension of differences in sexual development and other processes that are related to human reproduction and fertility, particularly those that involve androgen excess as consequence of their impairment.

APA, Harvard, Vancouver, ISO, and other styles

2

Bouguen, Guillaume, Laurent Dubuquoy, Pierre Desreumaux, Thomas Brunner, and Benjamin Bertin. "Intestinal steroidogenesis." Steroids 103 (November 2015): 64–71. http://dx.doi.org/10.1016/j.steroids.2014.12.022.

Full text

APA, Harvard, Vancouver, ISO, and other styles

3

Whitehouse, B. J. "Benzodiazepines and steroidogenesis." Journal of Endocrinology 134, no. 1 (July 1992): 1–3. http://dx.doi.org/10.1677/joe.0.1340001.

Full text

APA, Harvard, Vancouver, ISO, and other styles

4

Bornstein, S. R., H. Rutkowski, and I. Vrezas. "Cytokines and steroidogenesis." Molecular and Cellular Endocrinology 215, no. 1-2 (February 2004): 135–41. http://dx.doi.org/10.1016/j.mce.2003.11.022.

Full text

APA, Harvard, Vancouver, ISO, and other styles

5

Miller, Walter L. "Steroidogenesis: Unanswered Questions." Trends in Endocrinology & Metabolism 28, no. 11 (November 2017): 771–93. http://dx.doi.org/10.1016/j.tem.2017.09.002.

Full text

APA, Harvard, Vancouver, ISO, and other styles

6

Biason-Lauber, A., M. Boscaro, F. Mantero, and G. Balercia. "Defects of steroidogenesis." Journal of Endocrinological Investigation 33, no. 10 (February 24, 2010): 756–66. http://dx.doi.org/10.1007/bf03346683.

Full text

APA, Harvard, Vancouver, ISO, and other styles

7

Tesic, Biljana, Dragana Samardzija Nenadov, Tamara Tomanic, Svetlana Fa Nedeljkovic, Stevan Milatovic, Bojana Stanic, Kristina Pogrmic-Majkic, and Nebojsa Andric. "DEHP Decreases Steroidogenesis through the cAMP and ERK1/2 Signaling Pathways in FSH-Stimulated Human Granulosa Cells." Cells 12, no. 3 (January 22, 2023): 398. http://dx.doi.org/10.3390/cells12030398.

Full text

Abstract:

DEHP is an endocrine disruptor that interferes with the function of the female reproductive system. Several studies suggested that DEHP affects steroidogenesis in human and rodent granulosa cells (GC). Some studies have shown that DEHP can also affect the FSH-stimulated steroidogenesis in GC; however, the mechanism by which DEHP affects hormone-challenged steroidogenesis in human GC is not understood. Here, we analyzed the mechanism by which DEHP affects steroidogenesis in the primary culture of human cumulus granulosa cells (hCGC) stimulated with FSH. Cells were exposed to DEHP and FSH for 48 h, and steroidogenesis and the activation of cAMP and ERK1/2 were analyzed. The results show that DEHP decreases FSH-stimulated STAR and CYP19A1 expression, which is accompanied by a decrease in progesterone and estradiol production. DEHP lowers cAMP production and CREB phosphorylation in FSH but not cholera toxin- and forskolin-challenged hCGC. DEHP was not able to decrease steroidogenesis in cholera toxin- and forskolin-stimulated hCGC. Furthermore, DEHP decreases FSH-induced ERK1/2 phosphorylation. The addition of EGF rescued ERK1/2 phosphorylation in FSH- and DEHP-treated hCGC and prevented a decrease in steroidogenesis in the FSH- and DEHP-treated hCGC. These results suggest that DEHP inhibits the cAMP and ERK1/2 signaling pathways, leading to the inhibition of steroidogenesis in the FSH-stimulated hCGC.

APA, Harvard, Vancouver, ISO, and other styles

8

HUANG, BU‐MIIN, DOUGLAS M. STOCCO, and REID L. NORMAN. "The Cellular Mechanisms of Corticotropin‐Releasing Hormone (CRH)‐Stimulated Steroidogenesis in Mouse Leydig Cells Are Similar to Those for LH." Journal of Andrology 18, no. 5 (September 10, 1997): 528–34. http://dx.doi.org/10.1002/j.1939-4640.1997.tb01968.x.

Full text

Abstract:

ABSTRACT: Previous reports have demonstrated that corticotropin‐releasing hormone (CRH) treatment of primary cultures of mouse Leydig cells and MA‐10 mouse Leydig tumor cells results in a dose‐dependent stimulation of steroidogenesis, probably by acting through the cAMP/protein kinase A second messenger pathway. Based on this observation, the mechanism of CRH‐stimulated steroidogenesis is now further investigated and compared to trophic hormone stimulation. Both cell types were treated with human chorionic gonadotropin (hCG) or CRH in the absence and presence of the following agents: the translation inhibitor cycloheximide, the transcription inhibitor actinomycin D, the protonophore carbonyl cyanide m‐chlorophenylhydrozone (mCCCP), which disrupts the mitochondrial electrochemical gradient or the phorbol ester, phorbol‐12‐myristate 13‐acetate (PMA), a stimulator of protein kinase C. Cortico‐releasing hormone‐stimulated steroidogenesis was completely blocked by cycloheximide in both cell types, indicating that CRH‐stimulated steroidogenesis in mouse Leydig cells requires ongoing protein synthesis. Actinomycin D had profound inhibitory effects on CRH‐stimulated steroidogenesis in MA‐10 cells, and this inhibition was greater than that seen in mouse primary Leydig cells. mCCCP severely inhibited CRH‐stimulated steroid production in both cell types, indicating that an electrochemical gradient across the inner mitochondrial membrane is required for CRH‐stimulated steroidogenesis. In addition, PMA inhibited hCG‐ and CRH‐stimulated steroidogenesis in MA‐10 cells and CRH‐stimulated steroidogenesis in primary Leydig cells, suggesting that activation of the protein kinase C pathway can influence protein kinase A stimulated steroidogenesis. Results of these studies suggest that the mouse Leydig cell steroidogenic response to CRH shares many similarities to that of the LH response.

APA, Harvard, Vancouver, ISO, and other styles

9

de Mattos, Karine, Kenley Joule Pierre, and Jacques J. Tremblay. "Hormones and Signaling Pathways Involved in the Stimulation of Leydig Cell Steroidogenesis." Endocrines 4, no. 3 (August 1, 2023): 573–94. http://dx.doi.org/10.3390/endocrines4030041.

Full text

Abstract:

Leydig cells, located in the testis interstitial space, are the primary source of testosterone in males. Testosterone plays critical roles in both reproductive and metabolic functions and therefore is essential for male health. Steroidogenesis must be properly regulated since dysregulated hormone production can lead to infertility and metabolic disorders. Leydig cell steroidogenesis relies on the coordinated interaction of various factors, such as hormones and signaling molecules. While luteinizing hormone (LH) is the main regulator of Leydig cell steroidogenesis, other molecules, including growth hormones (GH), prolactin, growth factors (insulin, IGF, FGF, EGF), and osteocalcin, have also been implicated in the stimulation of steroidogenesis. This review provides a comprehensive summary of the mechanisms and signaling pathways employed by LH and other molecules in the stimulation of Leydig cell steroidogenesis, providing valuable insights into the complex regulation of male reproductive and metabolic health.

APA, Harvard, Vancouver, ISO, and other styles

10

Choi, M. S. K., and B. A. Cooke. "Calmidazolium is a potent stimulator of steroidogenesis via mechanisms not involving cyclic AMP, calcium or protein synthesis." Biochemical Journal 281, no. 1 (January 1, 1992): 291–96. http://dx.doi.org/10.1042/bj2810291.

Full text

Abstract:

This study reports an unexpected effect of calmidazolium on steroidogenesis. In contrast with previous work, which established that calmidazolium inhibits hormone-stimulated testosterone production in rat Leydig cells, the present study demonstrates that this compound is a potent stimulator of steroidogenesis when added by itself; this stimulation (approx. 10-fold in a 2 h incubation), was obtained over a narrow dose range (e.g.1-10 microM) in mouse and rat Leydig cells and in rat adrenocortical cells. The same concentrations of calmidazolium decreased basal cyclic AMP to undetectable levels in rat Leydig cells. Also, cyclic AMP stimulated with luteinizing hormone (LH), cholera toxin and forskolin was inhibited by calmidazolium (ED50 2 microM). In contrast with the actions of LH and cyclic AMP analogues on steroidogenesis, the effect of calmidazolium was not inhibited by removal of extracellular Ca2+, or by the addition of La3+ (a Ca(2+)-entry blocker), or the addition of cycloheximide (an inhibitor of protein translation). However, like dibutyryl cyclic AMP, calmidazolium-stimulated steroidogenesis was inhibited by aminoglutethimide, an inhibitor of cholesterol side-chain cleavage. Another calmodulin inhibitor, trifluoperazine, did not stimulate steroidogenesis. It is concluded that calmidazolium has a similar effect on steroidogenesis to LH, but by-passes the requirements for cyclic AMP, Ca2+, and protein synthesis. Calmidazolium is therefore a potentially important probe for elucidating the mechansims of control of steroidogenesis.

APA, Harvard, Vancouver, ISO, and other styles

11

He, H., AC Herington, and P. Roupas. "Effect of protein kinase C modulation on gonadotrophin-induced granulosa cell steroidogenesis." Reproduction, Fertility and Development 7, no. 1 (1995): 83. http://dx.doi.org/10.1071/rd9950083.

Full text

Abstract:

The effect of protein kinase C (PKC) modulation on gonadotrophin-induced ovarian granulosa cell differentiation was investigated by using an activator of PKC, phorbol 12-myristate 13-acetate (PMA) and inhibitors of PKC, sphingosine (SPH) and staurosporine (ST). The effects of PMA (at doses which activate PKC (10 ng mL-1), and down-regulate PKC (1000 ng mL-1)), sphingosine (25 microM) and staurosporine (10(-10)-10(-7) M) on gonadotrophin-induced granulosa cell differentiation were studied by the determination of steroidogenesis and cAMP accumulation in immature rat ovarian granulosa cells treated with or without pregnant mare serum gonadotrophin (100 mU mL-1). PMA (10 ng mL-1) inhibited gonadotrophin-induced granulosa cell steroidogenesis and cAMP accumulation. PMA (1000 ng mL-1)-induced down-regulation of PKC did not affect gonadotrophin-induced steroidogenesis. The inhibitory effect of PMA (10 ng mL-1) on gonadotrophin-induced granulosa cell steroidogenesis was not present in PKC-down-regulated cells. These data indicate that PKC activation by PMA inhibits gonadotrophin-induced steroidogenesis. SPH also inhibited gonadotrophin-induced steroidogenesis and cAMP accumulation. This effect of SPH was not affected by PMA-induced PKC down-regulation, indicating that this action of SPH does not require PKC or is mediated via a phorbol ester-insensitive PKC isoform. ST induced steroidogenesis in the absence of gonadotrophin, but was not synergistic with gonadotrophin. PMA-induced down-regulation of PKC abolished the effect of ST, suggesting that the action of ST requires PKC. The data suggest that ST and PMA, which antagonize each other in gonadotrophin-induced steroidogenesis, act via a PKC-mediated mechanism whereas the cAMP-associated actions of gonadotrophins and SPH are not dependent on PKC.

APA, Harvard, Vancouver, ISO, and other styles

12

Aqeilan, Rami I., John P. Hagan, Alain de Bruin, Maysoon Rawahneh, Zaidoun Salah, Eugenio Gaudio, Hasan Siddiqui, et al. "Targeted Ablation of the WW Domain-Containing Oxidoreductase Tumor Suppressor Leads to Impaired Steroidogenesis." Endocrinology 150, no. 3 (October 30, 2008): 1530–35. http://dx.doi.org/10.1210/en.2008-1087.

Full text

Abstract:

The WW domain-containing oxidoreductase (WWOX) gene encodes a 46-kDa tumor suppressor. The Wwox protein contains two N-terminal WW domains that interact with several transcriptional activators containing proline-tyrosine motifs and a central short-chain dehydrogenase/reductase domain that has been suggested to play a role in steroid metabolism. Recently, we have shown that targeted deletion of the Wwox gene in mice leads to postnatal lethality and defects in bone growth. Here, we report that Wwox-deficient mice display impaired steroidogenesis. Mutant homozygous mice are born with gonadal abnormalities, including failure of Leydig cell development in testis and reduced theca cell proliferation in ovary. Furthermore, Wwox−/− mice displayed impaired gene expression of key steroidogenesis enzymes. Affymetrix microarray gene analysis revealed differentially expressed related genes in steroidogenesis in knockout mice testis and ovary as compared with control mice. These results demonstrate the essential requirement for the Wwox tumor suppressor in proper steroidogenesis. The Wwox tumor suppressor is an essential requirement in proper steroidogenesis.

APA, Harvard, Vancouver, ISO, and other styles

13

Urbanek, Kinga Anna, Karolina Kowalska, Dominika Ewa Habrowska-Górczyńska, Marta Justyna Kozieł, Kamila Domińska, and Agnieszka Wanda Piastowska-Ciesielska. "Revealing the Role of Alternariol in the Local Steroidogenesis in Human Prostate Normal and Cancer Cells." International Journal of Molecular Sciences 24, no. 11 (May 30, 2023): 9513. http://dx.doi.org/10.3390/ijms24119513.

Full text

Abstract:

The mycotoxin alternariol (AOH) can be found in food products infected by Alternaria spp. and is considered an endocrine-disruptive mycotoxin. The main mechanism of AOH toxicity is associated with DNA damage and modulation of the inflammation process. Still, AOH is considered as one of the emerging mycotoxins. In this study, we have evaluated how AOH might affect the local steroidogenesis process in the prostate, in both normal and cancer cells. We have found that AOH itself modulates the cell cycle, inflammation, and apoptosis, rather than the steroidogenesis process in prostate cancer cells; however, in the presence of another steroidogenic agent, the influence on steroidogenesis is significant. Therefore, this is the first study to report the effect of AOH on local steroidogenesis in normal and prostate cancer cells. We postulate that AOH might modulate the release of the steroid hormones and expression of the key components by interfering with the steroidogenic pathway and might be considered a steroidogenesis-altering agent.

APA, Harvard, Vancouver, ISO, and other styles

14

Enangue Njembele, Annick N., and Jacques J. Tremblay. "Mechanisms of MEHP Inhibitory Action and Analysis of Potential Replacement Plasticizers on Leydig Cell Steroidogenesis." International Journal of Molecular Sciences 22, no. 21 (October 24, 2021): 11456. http://dx.doi.org/10.3390/ijms222111456.

Full text

Abstract:

Steroid production in Leydig cells is stimulated mainly by the pituitary luteinizing hormone, which leads to increased expression of genes involved in steroidogenesis, including the gene encoding the steroidogenic acute regulatory (STAR) protein. Mono(2-ethylhexyl)phthalate (MEHP), the active metabolite of the widely used plasticizer DEHP, is known to disrupt Leydig steroidogenesis but its mechanisms of action remain poorly understood. We found that MEHP caused a significant reduction in hormone-induced steroid hormone production in two Leydig cell lines, MA-10 and MLTC-1. Consistent with disrupted cholesterol transport, we found that MEHP represses cAMP-induced Star promoter activity. MEHP responsiveness was mapped to the proximal Star promoter, which contains multiple binding sites for several transcription factors. In addition to STAR, we found that MEHP also reduced the levels of ferredoxin reductase, a protein essential for electron transport during steroidogenesis. Finally, we tested new plasticizers as alternatives to phthalates. Two plasticizers, dioctyl succinate and 1,6-hexanediol dibenzoate, had no significant effect on hormone-induced steroidogenesis. Our current findings reveal that MEHP represses steroidogenesis by affecting cholesterol transport and its conversion into pregnenolone. We also found that two novel molecules with desirable plasticizer properties have no impact on Leydig cell steroidogenesis and could be suitable phthalate replacements.

APA, Harvard, Vancouver, ISO, and other styles

15

Bassi, Geetika, Simarjit Kaur Sidhu, and Suresh Mishra. "The Expanding Role of Mitochondria, Autophagy and Lipophagy in Steroidogenesis." Cells 10, no. 8 (July 22, 2021): 1851. http://dx.doi.org/10.3390/cells10081851.

Full text

Abstract:

The fundamental framework of steroidogenesis is similar across steroidogenic cells, especially in initial mitochondrial steps. For instance, the START domain containing protein-mediated cholesterol transport to the mitochondria, and its conversion to pregnenolone by the enzyme P450scc, is conserved across steroidogenic cells. The enzyme P450scc localizes to the inner mitochondrial membrane, which makes the mitochondria essential for steroidogenesis. Despite this commonality, mitochondrial structure, number, and dynamics vary substantially between different steroidogenic cell types, indicating implications beyond pregnenolone biosynthesis. This review aims to focus on the growing roles of mitochondria, autophagy and lipophagy in cholesterol uptake, trafficking and homeostasis in steroidogenic cells and consequently in steroidogenesis. We will focus on these aspects in the context of the physiological need for different steroid hormones and cell-intrinsic inherent features in different steroidogenic cell types beyond mitochondria as a mere site for the beginning of steroidogenesis. The overall goal is to provide an authentic and comprehensive review on the expanding role of steroidogenic cell-intrinsic processes in cholesterol homeostasis and steroidogenesis, and to bring attention to the scientific community working in this field on these promising advancements. Moreover, we will discuss a novel mitochondrial player, prohibitin, and its potential role in steroidogenic mitochondria and cells, and consequently, in steroidogenesis.

APA, Harvard, Vancouver, ISO, and other styles

16

Reyland, Mary E., David L. Williams, and Elizabeth K. White. "Inducible expression of protein kinase Cα suppresses steroidogenesis in Y-1 adrenocortical cells." American Journal of Physiology-Cell Physiology 275, no. 3 (September 1, 1998): C780—C789. http://dx.doi.org/10.1152/ajpcell.1998.275.3.c780.

Full text

Abstract:

We have previously shown that protein kinase C (PKC) suppresses steroidogenesis in Y-1 adrenocortical cells. To ask directly if the PKCα isoform mediates this suppression, we have developed Y-1 cell lines in which PKCα is expressed from a tetracycline-regulated promoter. Induction of PKCα expression in these cell lines results in decreased P450 cholesterol side-chain cleavage enzyme (P450-SCC) activity as judged by the conversion of hydroxycholesterol to pregnenolone. Transcription of a P450-SCC promoter-luciferase construct is also reduced when PKCα expression is increased. However, expression of PKCα has no effect on 8-bromo-cAMP induction of steroidogenesis, indicating that these pathways function independently to regulate steroidogenesis. To determine the relationship between endogenous PKC activity and steroidogenesis, we examined 12 Y-1 subclones that were isolated by limited dilution cloning. In each of these subclones, steroid production correlates inversely with total PKC activity and with the expression of PKCα but not PKCε or PKCζ. These studies define for the first time the role of a specific PKC isoform (PKCα) in regulating steroidogenesis and P450-SCC activity in adrenocortical cells.

APA, Harvard, Vancouver, ISO, and other styles

17

Sandor, Luca F., Reka Ragacs, and David S. Gyori. "Local Effects of Steroid Hormones within the Bone Microenvironment." International Journal of Molecular Sciences 24, no. 24 (December 14, 2023): 17482. http://dx.doi.org/10.3390/ijms242417482.

Full text

Abstract:

Steroid hormone production via the adrenal cortex, gonads, and placenta (so-called glandular steroidogenesis) is responsible for the endocrine control of the body’s homeostasis and is organized by a feedback regulatory mechanism based on the hypothalamus–pituitary–steroidogenic gland axis. On the other hand, recently discovered extraglandular steroidogenesis occurring locally in different tissues is instead linked to paracrine or autocrine signaling, and it is independent of the control by the hypothalamus and pituitary glands. Bone cells, such as bone-forming osteoblasts, osteoblast-derived osteocytes, and bone-resorbing osteoclasts, respond to steroid hormones produced by both glandular and extraglandular steroidogenesis. Recently, new techniques to identify steroid hormones, as well as synthetic steroids and steroidogenesis inhibitors, have been introduced, which greatly empowered steroid hormone research. Based on recent literature and new advances in the field, here we review the local role of steroid hormones in regulating bone homeostasis and skeletal lesion formation. The novel idea of extraglandular steroidogenesis occurring within the skeletal system raises the possibility of the development of new therapies for the treatment of bone diseases.

APA, Harvard, Vancouver, ISO, and other styles

18

Sullivan, M. H., and B. A. Cooke. "Effects of calmodulin and lipoxygenase inhibitors on LH (lutropin)- and LHRH (luliberin)-agonist-stimulated steroidogenesis in rat Leydig cells." Biochemical Journal 232, no. 1 (November 15, 1985): 55–59. http://dx.doi.org/10.1042/bj2320055.

Full text

Abstract:

The results of this study, carried out with purified rat Leydig cells, indicate that there are no major differences in the stimulating effects of lutropin (LH) and luliberin (LHRH) agonists on steroidogenesis via mechanisms that are dependent on Ca2+. This was demonstrated by using inhibitors of calmodulin and the lipoxygenase pathways of arachidonic acid metabolism. All three calmodulin inhibitors used (calmidazolium, trifluoperazine and chlorpromazine) were shown to block LH- and LHRH-agonist-stimulated steroidogenesis. This probably occurred at the step of cholesterol transport to the mitochondria. Similarly, three lipoxygenase inhibitors (nordihydroguaiaretic acid, BW755c and benoxaprofen), inhibited both LH- and LHRH-agonist-stimulated steroidogenesis. The amounts of the inhibitors required were similar for LH- and LHRH-agonist-stimulated steroidogenesis. Steroidogenesis stimulated by the Ca2+ ionophore A23187 was also inhibited, but higher concentrations of the inhibitors were required. Indomethacin (a cyclo-oxygenase inhibitor) increased LHRH-agonist-stimulated steroidogenesis;this is consistent with the role of the products of arachidonic acid metabolism via the alternative, lipoxygenase, pathway. The potentiation of LH-stimulated testosterone production by LHRH agonist was unaffected by indomethacin or by lipoxygenase inhibitors at concentrations that inhibited LH-stimulated testosterone production by 75-100%. It was not possible to eliminate a role of calmodulin in modulating the potentiation, although higher concentrations of the inhibitors were generally required to negate the potentiation than to inhibit LH- or LHRH-agonist-stimulated testosterone production.

APA, Harvard, Vancouver, ISO, and other styles

19

Shimizu-Albergine, Masami, Brian Van Yserloo, Martin G. Golkowski, Shao-En Ong, Joseph A. Beavo, and Karin E. Bornfeldt. "SCAP/SREBP pathway is required for the full steroidogenic response to cyclic AMP." Proceedings of the National Academy of Sciences 113, no. 38 (September 6, 2016): E5685—E5693. http://dx.doi.org/10.1073/pnas.1611424113.

Full text

Abstract:

Luteinizing hormone (LH) stimulates steroidogenesis largely through a surge in cyclic AMP (cAMP). Steroidogenic rates are also critically dependent on the availability of cholesterol at mitochondrial sites of synthesis. This cholesterol is provided by cellular uptake of lipoproteins, mobilization of intracellular lipid, and de novo synthesis. Whether and how these pathways are coordinated by cAMP are poorly understood. Recent phosphoproteomic analyses of cAMP-dependent phosphorylation sites in MA10 Leydig cells suggested that cAMP regulates multiple steps in these processes, including activation of the SCAP/SREBP pathway. SCAP [sterol-regulatory element-binding protein (SREBP) cleavage-activating protein] acts as a cholesterol sensor responsible for regulating intracellular cholesterol balance. Its role in cAMP-mediated control of steroidogenesis has not been explored. We used two CRISPR (clustered regularly interspaced short palindromic repeat)-Cas9 (CRISPR associated protein 9) knockout approaches to test the role of SCAP in steroidogenesis. Our results demonstrate that SCAP is required for progesterone production induced by concurrent inhibition of the cAMP phosphodiesterases PDE4 and PDE8. These inhibitors increased SCAP phosphorylation, SREBP2 activation, and subsequent expression of cholesterol biosynthetic genes, whereas SCAP deficiency largely prevented these effects. Reexpression of SCAP in SCAP-deficient cells restored SREBP2 protein expression and partially restored steroidogenic responses, confirming the requirement of SCAP–SREBP2 in steroidogenesis. Inhibitors of 3-hydroxy-3-methylglutaryl-Coenzyme A reductase and isoprenylation attenuated, whereas exogenously provided cholesterol augmented, PDE inhibitor-induced steroidogenesis, suggesting that the cholesterol substrate needed for steroidogenesis is provided by both de novo synthesis and isoprenylation-dependent mechanisms. Overall, these results demonstrate a novel role for LH/cAMP in SCAP/SREBP activation and subsequent regulation of steroidogenesis.

APA, Harvard, Vancouver, ISO, and other styles

20

Finco, Isabella, Christopher R. LaPensee, Kenneth T. Krill, and Gary D. Hammer. "Hedgehog Signaling and Steroidogenesis." Annual Review of Physiology 77, no. 1 (February 10, 2015): 105–29. http://dx.doi.org/10.1146/annurev-physiol-061214-111754.

Full text

APA, Harvard, Vancouver, ISO, and other styles

21

Costa, Barbara, Eleonora Da Pozzo, and Claudia Martini. "Translocator protein and steroidogenesis." Biochemical Journal 475, no. 5 (March 6, 2018): 901–4. http://dx.doi.org/10.1042/bcj20170766.

Full text

Abstract:

Two interesting papers by Barren et al. and Owen et al. have been very recently published in Biochemical Journal, reporting the role of translocator protein (TSPO) in steroidogenesis. The involvement of TSPO in the steroid biosynthesis has been suggested by 30 years of researches, using biochemical, pharmacological and genetic experimental approaches. In the last 3 years, however, the TSPO involvement in steroidogenesis has been intensively and profoundly discussed. Using in vivo genetic manipulations aimed at deleting TSPO, some researchers have excluded its role in steroid production. Other research groups, using similar genetic manipulation techniques, have presented different results, corroborating the role of TSPO in steroidogenesis, in particular, when hormonal stimulation occurs. In this scenario, the publications by Barron et al. about ‘Steroidogenic abnormalities in translocator protein knockout mice and significance in the aging male’ and by Owen et al. about ‘TSPO mutations in rats and a human polymorphism impair the rate of steroid synthesis’ are part of this debate and provide further and more accurate information supporting the importance of TSPO as a steroidogenesis regulator.

APA, Harvard, Vancouver, ISO, and other styles

22

Drucker, Susan, and Maria I. New. "Disorders of Adrenal Steroidogenesis." Pediatric Clinics of North America 34, no. 4 (August 1987): 1055–66. http://dx.doi.org/10.1016/s0031-3955(16)36302-7.

Full text

APA, Harvard, Vancouver, ISO, and other styles

23

New, Maria I. "Inborn Errors of Steroidogenesis." Steroids 63, no. 5-6 (May 1998): 238–42. http://dx.doi.org/10.1016/s0039-128x(98)00028-2.

Full text

APA, Harvard, Vancouver, ISO, and other styles

24

Sharpe, Richard M. "Intratesticular Control Of Steroidogenesis." Clinical Endocrinology 33, no. 6 (December 1990): 787–807. http://dx.doi.org/10.1111/j.1365-2265.1990.tb03916.x.

Full text

APA, Harvard, Vancouver, ISO, and other styles

25

Omura, Tsuneo, and Ken-ichirou Morohashi. "Gene regulation of steroidogenesis." Journal of Steroid Biochemistry and Molecular Biology 53, no. 1-6 (June 1995): 19–25. http://dx.doi.org/10.1016/0960-0760(95)00036-y.

Full text

APA, Harvard, Vancouver, ISO, and other styles

26

Luft, Friedrich C. "Steroidogenesis and CYP enzymes." Journal of Molecular Medicine 79, no. 10 (August 23, 2001): 549–50. http://dx.doi.org/10.1007/s001090100277.

Full text

APA, Harvard, Vancouver, ISO, and other styles

27

Miller, William R., and John O'Neill. "Mammary steroidogenesis: Therapeutic implications." International Journal of Radiation Applications and Instrumentation. Part B. Nuclear Medicine and Biology 14, no. 4 (January 1987): 369–75. http://dx.doi.org/10.1016/0883-2897(87)90014-6.

Full text

APA, Harvard, Vancouver, ISO, and other styles

28

Petrino, Teresa R., Yu-Wai Peter Lin, and Robin A. Wallace. "Steroidogenesis in Fundulus heteroclitus." General and Comparative Endocrinology 73, no. 1 (January 1989): 147–56. http://dx.doi.org/10.1016/0016-6480(89)90065-8.

Full text

APA, Harvard, Vancouver, ISO, and other styles

29

Petrino, Teresa R., M. S. Greeley, K. Selman, Y. W. P. Lin, and R. A. Wallace. "Steroidogenesis in Fundulus heteroclitus." General and Comparative Endocrinology 76, no. 2 (November 1989): 230–40. http://dx.doi.org/10.1016/0016-6480(89)90154-8.

Full text

APA, Harvard, Vancouver, ISO, and other styles

30

Magalhães, Manuel M., and Maria C. Magalhães. "Peroxisomes in adrenal steroidogenesis." Microscopy Research and Technique 36, no. 6 (March 15, 1997): 493–502. http://dx.doi.org/10.1002/(sici)1097-0029(19970315)36:6<493::aid-jemt6>3.0.co;2-j.

Full text

APA, Harvard, Vancouver, ISO, and other styles

31

Maniere, G., E. Vanhems, F. Gautron, and JP Delbecque. "Calcium inhibits ovarian steroidogenesis in the blowfly Phormia regina." Journal of Endocrinology 173, no. 3 (June 1, 2002): 533–44. http://dx.doi.org/10.1677/joe.0.1730533.

Full text

Abstract:

Calcium is frequently involved in the stimulation of steroidogenesis in gonads and endocrine glands, generally in association with cAMP. However, our present observations show that it has the opposite effect in the ovary of the blowfly Phormia regina. Our in vitro experiments first showed that extracellular calcium does not play a role during the stimulation of steroidogenesis in fly ovaries; indeed steroidogenesis was activated in vitro as efficiently in a medium with or without calcium, either by pharmacological compounds mimicking cAMP signaling or by active brain extracts. When calcium was experimentally introduced into biosynthetic cells by ionophores or liberated from internal stores by thapsigargin, it did not activate, but clearly inhibited both basal and acute steroidogenesis respectively in previtellogenic and in vitellogenic ovaries. Our experiments also demonstrated that calcium decreases cAMP concentrations in the ovaries of Phormia, by stimulating its degradation, without modifying its biosynthesis. Moreover, inhibitors of calcium-calmodulin phosphodiesterases (PDEs) increased steroid biosynthesis in vitro, whereas inhibitors of calcium-insensitive PDEs did not. These data thus demonstrate that, in blowfly ovaries, calcium ions inhibit cAMP-stimulated steroidogenesis by activating a calmodulin-sensitive (type I) PDE.

APA, Harvard, Vancouver, ISO, and other styles

32

Demmouche, Zoheir B., and Jacques J. Tremblay. "Comprehensive and Quantitative Analysis of the Changes in Proteomic and Phosphoproteomic Profiles during Stimulation and Repression of Steroidogenesis in MA-10 Leydig Cells." International Journal of Molecular Sciences 23, no. 21 (October 25, 2022): 12846. http://dx.doi.org/10.3390/ijms232112846.

Full text

Abstract:

Leydig cells produce testosterone, a hormone essential for male sex differentiation and spermatogenesis. The pituitary hormone, LH, stimulates testosterone production in Leydig cells by increasing the intracellular cAMP levels, which leads to the activation of various kinases and transcription factors, ultimately stimulating the expression of the genes involved in steroidogenesis. The second messenger, cAMP, is subsequently degraded to AMP, and the increase in the intracellular AMP levels activates AMP-dependent protein kinase (AMPK). Activated AMPK potently represses steroidogenesis. Despite the key roles played by the various stimulatory and inhibitory kinases, the proteins phosphorylated by these kinases during steroidogenesis remain poorly characterized. In the present study, we have used a quantitative LC-MS/MS approach, using total and phosphopeptide-enriched proteins to identify the global changes that occur in the proteome and phosphoproteome of MA-10 Leydig cells during both the stimulatory phase (Fsk/cAMP treatment) and inhibitory phase (AICAR-mediated activation of AMPK) of steroidogenesis. The phosphorylation levels of several proteins, including some never before described in Leydig cells, were significantly altered during the stimulation and inhibition of steroidogenesis. Our data also provide new key insights into the finely tuned and dynamic processes that ensure adequate steroid hormone production.

APA, Harvard, Vancouver, ISO, and other styles

33

Suyama, Atsuhito, Nahoko Iwata, Yoshiaki Soejima, Yasuhiro Nakano, Koichiro Yamamoto, Takahiro Nada, and Fumio Otsuka. "Involvement of NR5A1 and NR5A2 in the Regulation of Steroidogenesis by Clock Gene and BMPs by Human Granulosa Cells." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A768. http://dx.doi.org/10.1210/jendso/bvab048.1562.

Full text

Abstract:

Abstract We previously reported that the expression levels of Clock gene are linked to the expression levels of steroidogenetic enzymes in human granulosa cells (EJ 2019). However, the downstream molecules of the Clock gene actions in the regulation of ovarian steroidogenesis have yet to be elucidated. In the present study, we investigated the roles of the transcription factors, NR5A1 (also known as SF-1) and NR5A2 (LRH-1), which play key roles in the reproductive function as well as steroidogenesis by focusing on the functional link between Clock gene and bone morphogenetic protein (BMP) signaling using human granulosa KGN cells. First of all, we examined the effects of BMPs/growth differentiation factor (GDF) on forskolin (FSK)-induced steroidogenesis. As a result, FSK-induced mRNA levels of StAR and P450scc, but not P450arom, were potently suppressed by treatments with BMP-6, -9, -15 and GDF-9. The expression levels of NR5A1 and NR5A2 mRNA were also upregulated by FSK treatment, while the BMP-target gene Id-1 mRNA levels were stimulated by the treatment with BMPs. Of interest, treatments with BMPs/GDF increased FSK-induced NR5A1 mRNA levels but suppressed FSK-induced NR5A2 mRNA levels by granulosa cells. The expression levels of NR5A1 mRNA were positively correlated with the changes of P450arom and 3βHSD mRNA, whereas the expression levels of NR5A2 mRNA were correlated with that of StAR and P450scc mRNA. In addition, the expression levels of NR5A1 and NR5A2 mRNAs were positively correlated with the levels of Clock mRNA. In particular, Clock mRNA levels showed highly positive correlation with the levels of NR5A2 mRNA compared with NR5A1 mRNA. Of note, Id-1 mRNA levels were positively correlated with the levels of NR5A1 mRNA, but negatively correlated with that of NR5A2 mRNA. Furthermore, the inhibition of Clock gene expression by siRNA attenuated the expression levels of NR5A1 and NR5A2 mRNA, resulting in decreased mRNA levels of StAR and P450arom in the presence of FSK. Thus, the present results suggested a novel mechanism by which Clock expression is functionally linked to the expression of NR5A1 and NR5A2, the latter of which is further regulated by BMP signaling by granulosa cells. The interaction among Clock, NR5A1/NR5A2 and BMPs may be involved in the fine tuning of steroidogenesis by ovarian follicles.

APA, Harvard, Vancouver, ISO, and other styles

34

Zhang, Lihan, Qiushi Yang, Weitong Xu, Zhaojun Wu, and Dapeng Li. "Integrated Analysis of miR-430 on Steroidogenesis-Related Gene Expression of Larval Rice Field Eel Monopterus albus." International Journal of Molecular Sciences 22, no. 13 (June 29, 2021): 6994. http://dx.doi.org/10.3390/ijms22136994.

Full text

Abstract:

The present study aims to reveal the mechanism by which miR-430s regulate steroidogenesis in larval rice field eel Monopterus albus. To this end, M. albus embryos were respectively microinjected with miRNA-overexpressing mimics (agomir430a, agomir430b, and agomir430c) or miRNA-knockdown inhibitors (antagomir430a, antagomir430b, and antagomir430c). Transcriptome profiling of the larvae indicated that a total of more than 149 differentially expressed genes (DEGs) were identified among the eight treatments. Specifically, DEGs related to steroidogenesis, the GnRH signaling pathway, the erbB signaling pathway, the Wnt signaling pathway, and other pathways were characterized in the transcriptome. We found that steroidogenesis-related genes (hydroxysteroid 17-beta dehydrogenase 3 (17β-hsdb3), hydroxysteroid 17-beta dehydrogenase 7 (17β-hsdb7), hydroxysteroid 17-beta dehydrogenase 12 (17β-hsdb12), and cytochrome P450 family 19 subfamily a (cyp19a1b)) were significantly downregulated in miR-430 knockdown groups. The differential expressions of miR-430 in three gonads indicated different roles of three miR-430 (a, b, and c) isoforms in regulating steroidogenesis and sex differentiation. Mutation of the miR-430 sites reversed the downregulation of cytochrome P450 family 17 (cyp17), cyp19a1b, and forkhead box L2 (foxl2) reporter activities by miR-430, indicating that miR-430 directly interacted with cyp17, cyp19a1b, and foxl2 genes to inhibit their expressions. Combining these findings, we concluded that miR-430 regulated the steroidogenesis and the biosynthesis of steroid hormones by targeting cyp19a1b in larval M. albus. Our results provide a novel insight into steroidogenesis at the early stage of fish at the molecular level.

APA, Harvard, Vancouver, ISO, and other styles

35

Jones, PM, SB Sayed, SJ Persaud, CJ Burns, S. Gyles, and BJ Whitehouse. "Cyclic AMP-induced expression of steroidogenic acute regulatory protein is dependent upon phosphoprotein phosphatase activities." Journal of Molecular Endocrinology 24, no. 2 (April 1, 2000): 233–39. http://dx.doi.org/10.1677/jme.0.0240233.

Full text

Abstract:

In addition to the well-documented role of protein kinases in the regulation of steroid production, phosphoprotein phosphatase (PP) activity is required for steroidogenesis. In the present study, we have used the mouse Y1 adrenocortical cell line to identify the site of action of PPs on steroid production by measuring the effects of PP inhibition on the expression of the steroidogenic acute regulatory (StAR) protein and on steroid production. Forskolin-induced activation of cyclic AMP-dependent protein kinase (PKA) enhanced steroidogenesis and this was accompanied by an increased expression of StAR protein. Both steroidogenesis and StAR protein expression were inhibited by two structurally dissimilar inhibitors of PP1 and PP2A activities, okadaic acid and calyculin A. These results suggest that inhibition of PP1 and PP2A inhibits steroid production by preventing the expression of the StAR protein, implicating PP1/2A dephosphorylation reactions as important regulators of stimulus-dependent StAR protein expression, and thus of steroidogenesis.

APA, Harvard, Vancouver, ISO, and other styles

36

Maniere, G., I. Rondot, EE Bullesbach, F. Gautron, E. Vanhems, and JP Delbecque. "Control of ovarian steroidogenesis by insulin-like peptides in the blowfly (Phormia regina)." Journal of Endocrinology 181, no. 1 (April 1, 2004): 147–56. http://dx.doi.org/10.1677/joe.0.1810147.

Full text

Abstract:

This study investigated the ability of insulin and of insect insulin-like peptides (ILPs) to stimulate ovarian steroidogenesis in the blowfly Phormia regina. Bovine insulin was active on ovaries isolated in vitro, which showed an age-dependent sensitivity; this peptide progressively stimulated steroidogenesis in ovaries isolated from the third day after adult molt, but not in younger ones, and had maximal activity after the fifth day. This stimulatory effect was observed equally from females reared in the presence or in the absence of males, excluding a regulatory effect of mating. The mode of action of insulin in blowflies did not involve cAMP, but triggered a specific and well-conserved transduction cascade. In particular, a peroxovanadium compound, known to activate specifically the insulin receptor in mammals, also stimulated blowfly ovarian steroidogenesis in vitro. Conversely, chemicals known to inhibit the mammalian insulin receptor or downstream elements of its signaling pathway, such as LY294002, an inhibitor of phosphatidylinositol 3-kinase (PI3K), were able to prevent the steroidogenic action of bovine insulin on fly ovaries. Extracts from the median neurosecretory cells (MNCs) of blowfly brains, which are known to contain endogenous ILPs, stimulated ovarian steroidogenesis very efficiently and were also sensitive to inhibition by LY294002. These experiments indicated the involvement of PI3K in the mode of action of MNC extracts and substantiated that their endogenous ILPs are involved in the regulation of ovarian steroidogenesis. This conclusion was corroborated by the effects of synthetic bombyxin II, an ILP originating from silkworm MNCs, which also stimulated steroidogenesis in isolated blowfly ovaries. Altogether, these data suggest that insulinlike neurohormones from MNCs play a crucial role as steroidogenic gonadotropins in female flies.

APA, Harvard, Vancouver, ISO, and other styles

37

Bakhtyukov, Andrey A., Kira V. Derkach, Viktor N. Sorokoumov, Anna M. Stepochkina, Irina V. Romanova, Irina Yu Morina, Irina O. Zakharova, Liubov V. Bayunova, and Alexander O. Shpakov. "The Effects of Separate and Combined Treatment of Male Rats with Type 2 Diabetes with Metformin and Orthosteric and Allosteric Agonists of Luteinizing Hormone Receptor on Steroidogenesis and Spermatogenesis." International Journal of Molecular Sciences 23, no. 1 (December 24, 2021): 198. http://dx.doi.org/10.3390/ijms23010198.

Full text

Abstract:

In men with type 2 diabetes mellitus (T2DM), steroidogenesis and spermatogenesis are impaired. Metformin and the agonists of luteinizing hormone/human chorionic gonadotropin(hCG)-receptor (LH/hCG-R) (hCG, low-molecular-weight allosteric LH/hCG-R-agonists) can be used to restore them. The aim was to study effectiveness of separate and combined administration of metformin, hCG and 5-amino-N-tert-butyl-2-(methylsulfanyl)-4-(3-(nicotinamido)phenyl)thieno[2,3-d]pyrimidine-6-carboxamide (TP3) on steroidogenesis and spermatogenesis in male rats with T2DM. hCG (15 IU/rat/day) and TP3 (15 mg/kg/day) were injected in the last five days of five-week metformin treatment (120 mg/kg/day). Metformin improved testicular steroidogenesis and spermatogenesis and restored LH/hCG-R-expression. Compared to control, in T2DM, hCG stimulated steroidogenesis and StAR-gene expression less effectively and, after five-day administration, reduced LH/hCG-R-expression, while TP3 effects changed weaker. In co-administration of metformin and LH/hCG-R-agonists, on the first day, stimulating effects of LH/hCG-R-agonists on testosterone levels and hCG-stimulated expression of StAR- and CYP17A1-genes were increased, but on the 3–5th day, they disappeared. This was due to reduced LH/hCG-R-gene expression and increased aromatase-catalyzed estradiol production. With co-administration, LH/hCG-R-agonists did not contribute to improving spermatogenesis, induced by metformin. Thus, in T2DM, metformin and LH/hCG-R-agonists restore steroidogenesis and spermatogenesis, with metformin being more effective in restoring spermatogenesis, and their co-administration improves LH/hCG-R-agonist-stimulating testicular steroidogenesis in acute but not chronic administration.

APA, Harvard, Vancouver, ISO, and other styles

38

Mattar, D., M. Samir, M. Laird, and P. G. Knight. "Modulatory effects of TGF-β1 and BMP6 on thecal angiogenesis and steroidogenesis in the bovine ovary." Reproduction 159, no. 4 (April 2020): 397–408. http://dx.doi.org/10.1530/rep-19-0311.

Full text

Abstract:

Angiogenesis plays an integral role in follicular and luteal development and is positively regulated by several intra-ovarian factors including vascular endothelial growth factor A (VEGFA) and fibroblast growth factor 2 (FGF2). Various transforming growth factor-β (TGF-β) superfamily members function as intra-ovarian regulators of follicle and luteal function, but their potential roles in modulating ovarian angiogenesis have received little attention. In this study, we used a bovine theca interna culture model (exhibiting characteristics of luteinization) to examine the effects of TGF-β1 and bone morphogenetic protein 6 (BMP6) on angiogenesis and steroidogenesis. VEGFA/FGF2 treatment promoted endothelial cell network formation but had little or no effect on progesterone and androstenedione secretion or expression of key steroidogenesis-related genes. TGF-β1 suppressed basal and VEGFA/FGF2-induced endothelial cell network formation and progesterone secretion, effects that were reversed by an activin receptor-like kinase 5 (ALK5) inhibitor (SB-431542). The ALK5 inhibitor alone raised androstenedione secretion and expression of several transcripts including CYP17A1. BMP6 also suppressed endothelial cell network formation under VEGFA/FGF2-stimulated conditions and inhibited progesterone secretion and expression of several steroidogenesis-related genes under basal and VEGFA/FGF2-stimulated conditions. These effects were reversed by an ALK1/2 inhibitor (K02288). Moreover, the ALK1/2 inhibitor alone augmented endothelial network formation, progesterone secretion, androstenedione secretion and expression of several steroidogenesis-related genes. The results indicate dual suppressive actions of both TGF-β1 and BMP6 on follicular angiogenesis and steroidogenesis. Further experiments are needed to unravel the complex interactions between TGF-β superfamily signalling and other regulatory factors controlling ovarian angiogenesis and steroidogenesis.

APA, Harvard, Vancouver, ISO, and other styles

39

Gunnarsson, David, Per Leffler, Emelie Ekwurtzel, Gunilla Martinsson, Kui Liu, and Gunnar Selstam. "Mono-(2-ethylhexyl) phthalate stimulates basal steroidogenesis by a cAMP-independent mechanism in mouse gonadal cells of both sexes." REPRODUCTION 135, no. 5 (May 2008): 693–703. http://dx.doi.org/10.1530/rep-07-0460.

Full text

Abstract:

Phthalates are widely used as plasticizers in a number of daily-life products. In this study, we investigated the influence of mono-(2-ethylhexyl) phthalate (MEHP), the active metabolite of the frequently used plasticizer di-(2-ethylhexyl) phthalate (DEHP), on gonadal steroidogenesisin vitro. MEHP (25–100 μM) stimulated basal steroid synthesis in a concentration-dependent manner in immortalized mouse Leydig tumor cells (MLTC-1). The stimulatory effect was also detected in KK-1 granulosa tumor cells. MEHP exposure did not influence cAMP or StAR protein levels and induced a gene expression profile of key steroidogenic proteins different from the one induced by human chorionic gonadotropin (hCG). Simultaneous treatment with MEHP and a p450scc inhibitor (aminoglutethimide) indicated that MEHP exerts its main stimulatory effect prior to pregnenolone formation. MEHP (10–100 μM) up-regulated hormone-sensitive lipase and 3-hydroxy-3-methylglutaryl coenzyme A reductase, suggesting that MEHP increases the amount of cholesterol available for steroidogenesis. Our data suggest that MEHP, besides its known inhibitory effect on hCG action, can directly stimulate gonadal steroidogenesis in both sexes through a cAMP- and StAR-independent mechanism. The anti-steroidogenic effect of DEHP has been proposed to cause developmental disorders such as hypospadias and cryptorchidism, whereas a stimulation of steroid synthesis may prematurely initiate the onset of puberty and theoretically affect the hypothalamic–pituitary–gonadal axis.

APA, Harvard, Vancouver, ISO, and other styles

40

Sarawi, Wedad S., Ahlam M. Alhusaini, Laila M. Fadda, Hatun A. Alomar, Awatif B. Albaker, Hanan K. Alghibiwi, Amjad S. Aljrboa, Areej M. Alotaibi, Iman H. Hasan, and Ayman M. Mahmoud. "Nano-Curcumin Prevents Copper Reproductive Toxicity by Attenuating Oxidative Stress and Inflammation and Improving Nrf2/HO-1 Signaling and Pituitary-Gonadal Axis in Male Rats." Toxics 10, no. 7 (June 30, 2022): 356. http://dx.doi.org/10.3390/toxics10070356.

Full text

Abstract:

Copper is essential for several cellular processes and is an important catalytic factor for many proteins. However, excess copper can provoke oxidative stress and reproductive toxicity. This study evaluated the effect of liposomal nano-curcumin (N-CUR) and CUR on testicular oxidative injury, inflammation, and apoptosis, and altered steroidogenesis and Nrf2/HO-1 signaling induced by copper sulfate (CuSO4). Rats received CuSO4 and N-CUR or CUR via oral gavage for 7 days. CuSO4 induced histopathological changes and altered pituitary-gonadal axis manifested by decreased serum gonadotropins and testosterone. Testicular steroidogenesis genes (StAR, 3β-HSD, CYP17A1, and 17β-HSD) and androgen receptor (AR) were downregulated in rats that received CuSO4. N-CUR and CUR prevented testicular tissue injury, increased circulating FSH, LH, and testosterone, and upregulated testicular steroidogenesis genes and AR. Additionally, N-CUR and CUR decreased testicular MDA, NO, NF-κB, iNOS, TNF-α, Bax, and caspase-3 while enhanced Bcl-2, Nrf2, and the antioxidants GSH, HO-1, SOD, and catalase. In conclusion, N-CUR and CUR prevented CuSO4-induced reproductive toxicity in male rats by suppressing oxidative injury and inflammatory response and boosting steroidogenesis, sex hormones, and Nrf2/HO-1 signaling. N-CUR was more effective in ameliorating tissue injury, oxidative stress, inflammation, and apoptosis and enhancing steroidogenesis and Nrf2/HO-1 than the native form.

APA, Harvard, Vancouver, ISO, and other styles

41

Yazawa, Takashi, Yoshitaka Imamichi, Toshio Sekiguchi, Kaoru Miyamoto, Junsuke Uwada, Md Rafiqul Islam Khan, Nobuo Suzuki, Akihiro Umezawa, and Takanobu Taniguchi. "Transcriptional Regulation of Ovarian Steroidogenic Genes: Recent Findings Obtained from Stem Cell-Derived Steroidogenic Cells." BioMed Research International 2019 (April 1, 2019): 1–13. http://dx.doi.org/10.1155/2019/8973076.

Full text

Abstract:

Ovaries represent one of the primary steroidogenic organs, producing estrogen and progesterone under the regulation of gonadotropins during the estrous cycle. Gonadotropins fluctuate the expression of various steroidogenesis-related genes, such as those encoding steroidogenic enzymes, cholesterol deliverer, and electronic transporter. Steroidogenic factor-1 (SF-1)/adrenal 4-binding protein (Ad4BP)/NR5A1 and liver receptor homolog-1 (LRH-1) play important roles in these phenomena via transcriptional regulation. With the aid of cAMP, SF-1/Ad4BP and LRH-1 can induce the differentiation of stem cells into steroidogenic cells. This model is a useful tool for studying the molecular mechanisms of steroidogenesis. In this article, we will provide insight into the transcriptional regulation of steroidogenesis-related genes in ovaries that are revealed from stem cell-derived steroidogenic cells. Using the cells derived from the model, novel SF-1/Ad4BP- and LRH-1-regulated genes were identified by combined DNA microarray and promoter tiling array analyses. The interaction of SF-1/Ad4BP and LRH-1 with transcriptional regulators in the regulation of ovarian steroidogenesis was also revealed.

APA, Harvard, Vancouver, ISO, and other styles

42

Wang, Qi, Arthur Leader, and Benjamin K. Tsang. "Inhibitory Roles of Prohibitin and Chemerin in FSH-Induced Rat Granulosa Cell Steroidogenesis." Endocrinology 154, no. 2 (December 18, 2012): 956–67. http://dx.doi.org/10.1210/en.2012-1836.

Full text

Abstract:

Follicular differentiation is a tightly regulated process involving various endocrine, autocrine, and paracrine factors. The biosynthesis of progesterone and estradiol in response to FSH involves the regulation of multiple steroidogenic enzymes, such as p450 cholesterol side-chain cleavage enzyme and aromatase. Here we demonstrated that prohibitin (PHB), a multifunctional protein, inhibits FSH-induced progesterone and estradiol secretion in rat granulosa cells. The mRNA abundances of cyp11a (coding p450 cholesterol side-chain cleavage enzyme) and cyp19 (coding aromatase) were also suppressed by PHB in a time-dependent manner. It is known that a novel adipokine chemerin suppresses FSH-induced steroidogenesis in granulosa cells. Chemerin up-regulates the content of PHB, and PHB knockdown attenuates the suppressive role of chemerin on steroidogenesis. In addition, inhibition of phosphatidylinositol 3-kinase/Akt pathway enhances the suppressive action of PHB, whereas expression of constitutively active Akt attenuates this response. These findings suggest that PHB is a novel negative regulator of FSH-induced steroidogenesis, and its action with chemerin may contribute to the dysregulation of steroidogenesis in the pathogenesis of polycystic ovarian syndrome.

APA, Harvard, Vancouver, ISO, and other styles

43

Tu, Lan N., Amy H. Zhao, Douglas M. Stocco, and Vimal Selvaraj. "PK11195 Effect on Steroidogenesis Is Not Mediated Through the Translocator Protein (TSPO)." Endocrinology 156, no. 3 (March 1, 2015): 1033–39. http://dx.doi.org/10.1210/en.2014-1707.

Full text

Abstract:

Abstract Translocator protein (TSPO) is a mitochondrial outer membrane protein of unknown function with high physiological expression in steroidogenic cells. Using TSPO gene–deleted mice, we recently demonstrated that TSPO function is not essential for steroidogenesis. The first link between TSPO and steroidogenesis was established in studies showing modest increases in progesterone production by adrenocortical and Leydig tumor cell lines after treatment with PK11195. To reconcile discrepancies between physiological and pharmacological interpretations of TSPO function, we generated TSPO-knockout MA-10 mouse Leydig tumor cells (MA-10:TspoΔ/Δ) and examined their steroidogenic potential after exposure to either dibutyryl-cAMP or PK11195. Progesterone production in MA-10:TspoΔ/Δ after dibutyryl-cAMP was not different from control MA-10:Tspo+/+ cells, confirming that TSPO function is not essential for steroidogenesis. Interestingly, when treated with increasing concentrations of PK11195, both control MA-10:Tspo+/+ cells and MA-10:TspoΔ/Δ cells responded in a similar dose-dependent manner showing increases in progesterone production. These results show that the pharmacological effect of PK11195 on steroidogenesis is not mediated through TSPO.

APA, Harvard, Vancouver, ISO, and other styles

44

Bakhtyukov, Andrey A., Kira V. Derkach, Maxim A. Gureev, Dmitry V. Dar’in, Viktor N. Sorokoumov, Irina V. Romanova, Irina Yu Morina, Anna M. Stepochkina, and Alexander O. Shpakov. "Comparative Study of the Steroidogenic Effects of Human Chorionic Gonadotropin and Thieno[2,3-D]pyrimidine-Based Allosteric Agonist of Luteinizing Hormone Receptor in Young Adult, Aging and Diabetic Male Rats." International Journal of Molecular Sciences 21, no. 20 (October 11, 2020): 7493. http://dx.doi.org/10.3390/ijms21207493.

Full text

Abstract:

Low-molecular-weight agonists of luteinizing hormone (LH)/human chorionic gonadotropin (hCG) receptor (LHCGR), which interact with LHCGR transmembrane allosteric site and, in comparison with gonadotropins, more selectively activate intracellular effectors, are currently being developed. Meanwhile, their effects on testicular steroidogenesis have not been studied. The purpose of this work is to perform a comparative study of the effects of 5-amino-N-tert-butyl-4-(3-(1-methylpyrazole-4-carboxamido)phenyl)-2-(methylthio)thieno[2,3-d] pyrimidine-6-carboxamide (TP4/2), a LHCGR allosteric agonist developed by us, and hCG on adenylyl cyclase activity in rat testicular membranes, testosterone levels, testicular steroidogenesis and spermatogenesis in young (four-month-old), aging (18-month-old) and diabetic male Wistar rats. Type 1 diabetes was caused by a single streptozotocin (50 mg/kg) injection. TP4/2 (20 mg/kg/day) and hCG (20 IU/rat/day) were administered for 5 days. TP4/2 was less effective in adenylyl cyclase stimulation and ability to activate steroidogenesis when administered once into rats. On the 3rd–5th day, TP4/2 and hCG steroidogenic effects in young adult, aging and diabetic rats were comparable. Unlike hCG, TP4/2 did not inhibit LHCGR gene expression and did not hyperstimulate the testicular steroidogenesis system, moderately increasing steroidogenic proteins gene expression and testosterone production. In aging and diabetic testes, TP4/2 improved spermatogenesis. Thus, during five-day administration, TP4/2 steadily stimulates testicular steroidogenesis, and can be used to prevent androgen deficiency in aging and diabetes.

APA, Harvard, Vancouver, ISO, and other styles

45

Spyroglou, Ariadni, Anna Riester, Katharina Mueller-Peltzer, Ailing Lu, Juliane Rohde, Constanze Hantel, Claudia Kuehne, et al. "Adrenal and Ovarian Phenotype of a Tissue-Specific Urocortin 2–Overexpressing Mouse Model." Endocrinology 156, no. 7 (May 5, 2015): 2646–56. http://dx.doi.org/10.1210/en.2014-1971.

Full text

Abstract:

Urocortin 2 (UCN2) is a neuropeptide of the CRH family, involved in homeostatic mechanisms, the stress response, and control of anxiety. To elucidate the effects of UCN2 on steroidogenesis, we developed a mouse model that allows a Cre recombinase–determined conditional overexpression of UCN2 (UCN2-COE). In these mice SF1-Cre-driven overexpression of UCN2 was restricted to the adrenal glands, gonads, and parts of the hypothalamus. UCN2-COE animals of both sexes revealed significantly higher plasma UCN2 levels and significantly higher UCN2 expression levels in the adrenals and ovaries. In contrast, the baseline expression of UCN2 was already high in the testes of control mice with no further increase achievable in UCN2-COE animals. Adrenal steroidogenesis of UCN2-COE animals was investigated under baseline conditions, upon an ACTH stimulation test, and following a restraint stress test. A tendency toward lower expression of steroidogenic enzymes was detectable in UCN2-COE animals of both sexes with slight differences between males and females. A similar reduction in the expression levels of the final steps of ovarian steroidogenesis, accompanied by reduced plasma estradiol levels, was observed in female UCN2-COE animals. Thus, adrenal UCN2 overexpression resulted in down-regulation of adrenal steroidogenesis, suggesting a reduction in the stress response in the mouse (stress coping behavior). Similarly, UCN2 overexpression in the ovaries caused a decrease in steroidogenesis and reduction of follicles that had undergone ovulation. Nevertheless, this finding was not associated with reduced fertility.

APA, Harvard, Vancouver, ISO, and other styles

46

Zilz, Alexandra, Hua Li, Rosa Castello, Vassilios Papadopoulos, and Eric P. Widmaier. "Developmental Expression of the Peripheral-Type Benzodiazepine Receptor and the Advent of Steroidogenesis in Rat Adrenal Glands*." Endocrinology 140, no. 2 (February 1, 1999): 859–64. http://dx.doi.org/10.1210/endo.140.2.6475.

Full text

Abstract:

Abstract Although the precise mechanism whereby cholesterol is transported across the outer mitochondrial membrane is uncertain, a multimeric receptor complex termed the peripheral-type benzodiazepine receptor (PBR) appears essential for this process. We therefore predicted that adrenal cells at different developmental stages would express PBR coincidentally with the advent of steroidogenesis. Adrenals of neonatal rats demonstrate greatly reduced sensitivity to ACTH that gradually increases after the first 2 weeks of life. Thus, neonates have lower circulating corticosterone levels following exposure to stress. We examined mitochondrial PBR ligand binding activity, immunoreactive (ir) PBR content, and adrenal sensitivity to ACTH in vivo and in vitro. Ontogeny of both mitochondrial PBR ligand binding capacity and irPBR directly paralleled that of ACTH-inducible steroidogenesis in isolated rat adrenal cells and in rats injected with ACTH. In addition, neonatal PBR had approximately 2-fold higher affinity for PK11195, a synthetic ligand that binds with high affinity to PBR. No correlation was observed during neonatal life between ir-steroidogenic acute regulatory (StAR) protein content and steroidogenesis. These results are consistent with the hypothesis that PBR is an absolute prerequisite for adrenocortical steroidogenesis, and suggest that the stress hyporesponsive period of neonatal rats may result from decreased PBR expression. In addition, the higher affinity of neonatal PBR and the relatively high basal expression of StAR protein in neonatal adrenals may partly explain the high constitutive steroidogenesis characteristic of neonatal rat adrenal cells.

APA, Harvard, Vancouver, ISO, and other styles

47

Ehrhart-Bornstem, M., S. R. Bornstein, J. González-Hernández, J. J. Holst, M. R. Waterman, and W. A. Scherbaum. "Sympathoadrenal regulation of adrenocortical steroidogenesis." Endocrine Research 21, no. 1-2 (January 1995): 13–24. http://dx.doi.org/10.3109/07435809509030417.

Full text

APA, Harvard, Vancouver, ISO, and other styles

48

Comstock, Clay E. S., and Karen E. Knudsen. "IGF2 revs the steroidogenesis engine." Endocrine-Related Cancer 20, no. 5 (July 1, 2013): C19—C21. http://dx.doi.org/10.1530/erc-13-0243.

Full text

Abstract:

Molecular understanding of how prostate cancers evade hormone therapy greatly increased over the last several years, and the realization that de novo steroidogenesis plays a significant role in tumor progression and therapeutic bypass has led to development of promising new therapeutics. In the April 2013 issue of Endocrine-Related Cancer, Lubik et al. revealed a new molecular pathway by which the IGF2 can ignite the de novo steroidogenesis engine and promote molecular events associated with tumor progression.

APA, Harvard, Vancouver, ISO, and other styles

49

Midzak, Andrew, Barry Zirkin, and Vassilios Papadopoulos. "Translocator protein: pharmacology and steroidogenesis." Biochemical Society Transactions 43, no. 4 (August 1, 2015): 572–78. http://dx.doi.org/10.1042/bst20150061.

Full text

Abstract:

The translocator protein (TSPO; 18k Da) is an evolutionarily conserved outer mitochondrial membrane (OMM) protein highly expressed in steroid-synthesizing cells and found to possess a number of physiological and drug-binding partners. Extensive pharmacological, biochemical and cell biological research over the years has led to a model of TSPO involvement in mitochondrial cholesterol transport and promotion of steroid synthesis, a model guiding the design of drugs useful in stimulating neurosteroid synthesis and alleviating psychopathological symptoms. The involvement of TSPO in these processes has been called into question; however, with the publication of TSPO-deletion mouse models which saw no changes in steroid production. Here, we review work characterizing TSPO in steroidogenesis and offer perspective to research into TSPO pharmacology and its involvement in steroid biosynthesis.

APA, Harvard, Vancouver, ISO, and other styles

50

Donadeu, F. X., S. D. Sontakke, and J. Ioannidis. "MicroRNA indicators of follicular steroidogenesis." Reproduction, Fertility and Development 29, no. 5 (2017): 906. http://dx.doi.org/10.1071/rd15282.

Full text

Abstract:

MicroRNAs (miRNAs) can provide useful biomarkers of tissue function. The aim of the present study was to determine, in bovine follicles (n = 66; diameter 4–22 mm), the relationship among several indices of steroidogenesis and levels of 15 miRNAs previously identified to be associated with follicle development. Oestradiol levels, the oestradiol : progesterone (E : P) ratio and cytochrome P450 family 19 subfamily A member 1 (CYP19A1) expression were strongly correlated with each other (ρ > 0.8) and with LH/choriogonadotropin receptor (LHCGR) expression (ρ ≥ 0.6; P < 0.01). Levels of nine different miRNAs in the follicular wall were correlated (P < 0.01) with oestradiol, the E : P ratio and CYP19A1, with miR-873 showing the strongest correlation in each case (ρ > 0.7). Analyses of follicular fluid miRNAs identified miR-202 as correlated with oestradiol, the E : P ratio and CYP19A1 (ρ > 0.5; P < 0.01). When considering all follicle end-points together, we found that using a cut-off value of E : P = 1 overestimated the number of oestrogen-inactive follicles, whereas using CYP19A1 as a classifier provided a clearer separation of follicle samples based on oestrogen activity, in agreement with the E : P ratio, LHCGR expression and levels of miR-873 and miR-202. In conclusion, we identified miR-873 and miR-202 as miRNAs whose levels in follicular tissues can be used as indicators of steroidogenic capacity in bovine. We showed that these or other gene expression parameters, in addition or alternatively to the E : P ratio, should be used to accurately classify follicles based on steroidogenic capacity.

APA, Harvard, Vancouver, ISO, and other styles

Journal articles on the topic 'Steroidogenesis'

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles