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.

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.

Expression of the steroidogenic acute regulatory protein mRNA in adrenal tumors and cultured adrenal cells

1996 ◽  
Vol 150 (1) ◽  
pp. 43-50 ◽  
Author(s):  
J Liu ◽  
P Heikkilä ◽  
A I Kahri ◽  
R Voutilainen
Keyword(s):  
Kinase Inhibitor ◽  
Regulatory Protein ◽  
Early Response ◽  
Steroidogenic Acute Regulatory Protein ◽  
Adrenal Tumors ◽  
Adrenocortical Cells ◽  
Mrna Accumulation ◽  
Chain Cleavage ◽  
Steroidogenic Acute Regulatory ◽  
Adrenocortical Carcinomas

Abstract The steroidogenic acute regulatory protein (StAR) has recently been shown to be a factor necessary for cholesterol transport into adrenal and gonadal mitochondria, which is the regulated, rate-limiting step in steroidogenesis. We show here that StAR mRNA is highly expressed in normal adult adrenals (n=9), adrenocortical adenomas (n=16), adrenal hyperplasias (n=6), adrenocortical carcinomas (n=6) and adrenals adjacent to tumor tissues (n=9). There was a good correlation between the expression of StAR and the cholesterol side-chain cleavage enzyme/20,22-desmolase (P450 scc) mRNAs both in normal (r=0·93; P<0·01) and in tumor (r=0·97; P<0·001) tissues. No StAR mRNA was detected in Northern blots of liver, kidney, breast, parathyroid or phaeochromocytoma RNAs. In cultured adrenocortical cells, adrenocorticotropin (ACTH), (Bu)2cAMP, and cholera toxin increased StAR and P450 scc mRNA accumulation 6- to 18-fold, dose-and time-dependently. StAR (and P450 scc) mRNA increased relatively slowly in response to ACTH treatment, with the maximal increment at 24 h, while the mRNA of the early response gene c-fos peaked within 2 h. The protein kinase inhibitor H-7 inhibited basal and ACTH-induced StAR mRNA expression. Our results show that StAR mRNA is expressed at high levels in normal human adrenals and adrenocortical neoplasms. It is up-regulated in parallel with P450 scc by ACTH in adult adrenocortical cells, which suggests that ACTH is at least one of the key regulators of adrenal StAR expression. Journal of Endocrinology (1996) 150, 43–50

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