Growth hormone regulates steroidogenic acute regulatory protein expression and steroidogenesis in Leydig cell progenitors.
Gonadal development and differentiation is dependent in part on GH, as GH deficiency has been implicated as a cause of lowered fertility and spermatogenic cessation in humans and some biological models. In this study, we demonstrate that GH receptor messenger RNA (mRNA) is preferentially expressed in progenitor Leydig cells (PLCs) isolated and purified from 21-day-old rats. GH induces significant increases in the levels of steroidogenic acute regulatory protein (StAR), 3beta-hydroxysteroid dehydrogenase (3beta-HSD) expression, and androgen production in PLCs. Additionally, the cytokine interferon-gamma (IFNgamma) markedly inhibits GH-stimulated StAR mRNA and protein levels. When cells are cultured with both GH and IFNgamma, IFNgamma decreases the stimulating effect of GH on androgen production. Treatment of PLCs with cycloheximide does not prevent the GH-induced StAR mRNA, indicating that GH induction of StAR transcripts does not require de novo protein synthesis. In contrast, the induction of 3beta-HSD mRNA by GH is altered by cycloheximide treatment. H7, a serine/threonine kinase inhibitor, completely abrogates the increases in StAR mRNA by GH, whereas the tyrosine kinase inhibitor genistein does not. Moreover, GH further enhances StAR and 3beta-HSD mRNA expression in isolated adult rat Leydig cells despite their increased basal expression subsequent to maturational acquisition of these steroidogenic components. These data provide the first demonstration of the direct effects of GH on testicular steroidogenesis during progenitor Leydig cell differentiation.
Kanzaki
M
M
Population Council, New York, New York 10021, USA.
Morris
P L
PL
D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000728:Androgens / Q000096:biosynthesis*; D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D015870:Gene Expression; D013006:Growth Hormone / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology; D007985:Leydig Cells / Q000378:metabolism*; D008297:Male; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011986:Receptors, Somatotropin / Q000235:genetics; D013234:Stem Cells / Q000378:metabolism*; D000098682:Steroidogenic Acute Regulatory Protein
D000728:Androgens; D006063:Chorionic Gonadotropin; D010750:Phosphoproteins; D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D000098682:Steroidogenic Acute Regulatory Protein; D007371:Interferon-gamma; D013006:Growth Hormone; D003513:Cycloheximide; D015096:3-Hydroxysteroid Dehydrogenases