scholarly journals Hormone-induced 14-3-3γ Adaptor Protein Regulates Steroidogenic Acute Regulatory Protein Activity and Steroid Biosynthesis in MA-10 Leydig Cells

2012 ◽  
Vol 287 (19) ◽  
pp. 15380-15394 ◽  
Author(s):  
Yasaman Aghazadeh ◽  
Malena B. Rone ◽  
Josip Blonder ◽  
Xiaoying Ye ◽  
Timothy D. Veenstra ◽  
...  
Keyword(s):  
Leydig Cells ◽  
Regulatory Protein ◽  
Adaptor Protein ◽  
Steroidogenic Acute Regulatory Protein ◽  
Steroid Biosynthesis ◽  
Protein Activity ◽  
Steroidogenic Acute Regulatory

scholarly journals Synergistic Activation of Steroidogenic Acute Regulatory Protein Expression and Steroid Biosynthesis by Retinoids: Involvement of cAMP/PKA Signaling

Endocrinology ◽  
2014 ◽  
Vol 155 (2) ◽  
pp. 576-591 ◽  
Author(s):  
Pulak R. Manna ◽  
Andrzej T. Slominski ◽  
Steven R. King ◽  
Cloyce L. Stetson ◽  
Douglas M. Stocco
Keyword(s):  
Retinoic Acid ◽  
Leydig Cells ◽  
Binding Protein ◽  
Regulatory Protein ◽  
Liver X Receptor ◽  
Steroidogenic Acute Regulatory Protein ◽  
Type I ◽  
Steroid Biosynthesis ◽  
Steroidogenic Acute Regulatory ◽  
Star Gene

Both retinoic acid receptors (RARs) and retinoid X receptors (RXRs) mediate the action of retinoids that play important roles in reproductive development and function, as well as steroidogenesis. Regulation of steroid biosynthesis is principally mediated by the steroidogenic acute regulatory protein (StAR); however, the modes of action of retinoids in the regulation of steroidogenesis remain obscure. In this study we demonstrate that all-trans retinoic acid (atRA) enhances StAR expression, but not its phosphorylation (P-StAR), and progesterone production in MA-10 mouse Leydig cells. Activation of the protein kinase A (PKA) cascade, by dibutyrl-cAMP or type I/II PKA analogs, markedly increased retinoid-responsive StAR, P-StAR, and steroid levels. Targeted silencing of endogenous RARα and RXRα, with small interfering RNAs, resulted in decreases in 9-cis RA-stimulated StAR and progesterone levels. Truncation of and mutational alterations in the 5′-flanking region of the StAR gene demonstrated the importance of the −254/−1-bp region in retinoid responsiveness. An oligonucleotide probe encompassing an RXR/liver X receptor recognition motif, located within the −254/−1-bp region, specifically bound MA-10 nuclear proteins and in vitro transcribed/translated RXRα and RARα in EMSAs. Transcription of the StAR gene in response to atRA and dibutyrl-cAMP was influenced by several factors, its up-regulation being dependent on phosphorylation of cAMP response-element binding protein (CREB). Chromatin immunoprecipitation studies revealed the association of phosphorylation of CREB, CREB binding protein, RXRα, and RARα to the StAR promoter. Further studies elucidated that hormone-sensitive lipase plays an important role in atRA-mediated regulation of the steroidogenic response that involves liver X receptor signaling. These findings delineate the molecular events by which retinoids influence cAMP/PKA signaling and provide additional and novel insight into the regulation of StAR expression and steroidogenesis in mouse Leydig cells.

scholarly journals Cyclooxygenase-2 and Prostaglandin F2α in Syrian Hamster Leydig Cells: Inhibitory Role on Luteinizing Hormone/Human Chorionic Gonadotropin-Stimulated Testosterone Production

Endocrinology ◽  
2006 ◽  
Vol 147 (9) ◽  
pp. 4476-4485 ◽  
Author(s):  
Mónica B. Frungieri ◽  
Silvia I. Gonzalez-Calvar ◽  
Fernanda Parborell ◽  
Martin Albrecht ◽  
Artur Mayerhofer ◽  
...  
Keyword(s):  
Chorionic Gonadotropin ◽  
Human Chorionic Gonadotropin ◽  
Syrian Hamster ◽  
Leydig Cells ◽  
Regulatory Protein ◽  
Hydroxysteroid Dehydrogenase ◽  
Steroidogenic Acute Regulatory Protein ◽  
Testosterone Production ◽  
Cox 2 ◽  
Steroidogenic Acute Regulatory

We have previously found that cyclooxygenase-2 (COX-2), a key enzyme in the biosynthesis of prostaglandins (PGs), is present in the testicular interstitial cells of infertile men, whereas it is absent in human testes with no evident morphological changes or abnormalities. To find an animal model for further investigating COX-2 and its role in testicular steroidogenesis, we screened testes from adult species ranging from mice to monkeys. By using immunohistochemical assays, we found COX-2 expression only in Leydig cells of the reproductively active (peripubertal, pubertal, and adult) seasonal breeder Syrian hamster. COX-2 expression in hamster Leydig cells was confirmed by RT-PCR. In contrast, COX-1 expression was not detected in hamster testes. Because COX-2 expression implies PG synthesis, we investigated the effect of various PGs on testosterone production and found that PGF2α stood out because it significantly reduced human chorionic gonadotropin-stimulated testosterone release from isolated hamster Leydig cells in a dose-dependent manner. This mechanism involves a decreased expression of testicular steroidogenic acute regulatory protein and 17β-hydroxysteroid dehydrogenase. Testicular concentration and content of PGF2α in reproductively active hamsters as well as production of PGF2α from isolated hamster Leydig cells were also determined. Moreover, PGF2α receptors were localized in Leydig cells of hamsters and testicular biopsies from patients with Sertoli cell only and germ arrest syndromes. Thus, in this study, we described a COX-2-initiated pathway that via PGF2α production, PGF2α receptors, steroidogenic acute regulatory protein, and 17β-hydroxysteroid dehydrogenase represents a physiological local inhibitory system of human chorionic gonadotropin-stimulated testosterone production in the Syrian hamster testes.

scholarly journals Regulation of Leydig cells through a steroidogenic acute regulatory protein-independent pathway by a lipophilic factor from macrophages

1998 ◽  
Vol 158 (2) ◽  
pp. 267-275 ◽  
Author(s):  
YO Lukyanenko ◽  
AM Carpenter ◽  
DE Brigham ◽  
DM Stocco ◽  
JC Hutson
Keyword(s):  
Leydig Cells ◽  
Regulatory Protein ◽  
High Capacity ◽  
Steroidogenic Acute Regulatory Protein ◽  
Maximal Response ◽  
Maximal Dose ◽  
Testosterone Production ◽  
Highly Active ◽  
Chain Cleavage ◽  
Steroidogenic Acute Regulatory

The purpose of this investigation was to study the mechanism of action of a macrophage-derived factor that stimulates steroid production by Leydig cells. This factor increased testosterone production within 30 min, and reached a half-maximal response by 6-8 h. At a maximal dose, it stimulated testosterone production 20-fold at 24 h. Its efficacy was consistently higher than that achieved with a maximal dose of human chorionic gonadotropin (hCG). However, Leydig cells treated with a maximal dose of both the macrophage-derived factor and hCG secreted the same amount of testosterone as when given a maximal dose of only the macrophage-derived factor. The macrophage-derived factor did not require new protein synthesis to stimulate testosterone production, nor did it alter the amount of steroidogenic acute regulatory protein (StAR). While the macrophage-derived factor required an active cholesterol side-chain cleavage complex system, it did not alter the capacity of this enzyme complex. Finally, the macrophage-derived factor was unable to stimulate the production of progesterone by isolated mitochondria. In summary, the macrophage-derived factor is a highly active, acute regulator of steroidogenesis that acts through a high capacity StAR-independent pathway.

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