TRANSCRIPTIONAL REGULATION OF THE LUTROPIN HUMAN CHORIOGONADOTROPIN RECEPTOR AND 3 ENZYMES OF STEROIDOGENESIS BY GROWTH-FACTORS IN CULTUREDPIG LEYDIG-CELLS/

Recent data have shown that Leydig-cell-specific functions, and theref ore steroidogenic capacity, can be regulated by lutropin/human choriog onadotropin collectively termed gonadotropin and by several growth fac tors that are produced by and act within the testis. However, the mole cular mechanisms by which these factors regulate Leydig cells are not understood. In the present study, we have investigated the effects of basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), insulin-like growth factor I (IGF-I) and transforming growth factor be ta (TGF-beta) on mRNA for the gonadotropin receptor and three steroido genic enzymes: cytochrome P450(scc), cytochrome P-450 17 alpha-hydroxy lase/C17-20 lyase (17 alpha-hydroxylase), and 3 beta-hydroxysteroid de hydrogenase. IGF-I, which can enhance testosterone production, increas ed gonadotropin-receptor density after an increase in receptor mRNA le vels, and it increased the level of mRNA for cytochrome P-450(scc) and 17 alpha-hydrolyase. Micromolar concentrations of insulin had similar effects to those of IGF-I. Moreover, the three factors that decreased testosterone production (EGF, bFGF and TGF beta 1) decreased gonadotr opin receptor density, receptor mRNA levels and the mRNA levels for 17 alpha-hydroxylase. The potential effects of these growth factors on t he transcription of the gonadotropin genes for the receptor and these three steroidogenic enzymes were measured by means of nuclear run-on a ssays. We demonstrated that the long-term inhibitory (EGF, bFGF, TGF b eta 1) or stimulatory (IGF-I) effects of these growth factors are prim arily due to a Variation in the transcription rates of genes for the g onadotropin receptor, cytochrome P-450(scc) and 17 alpha-hydroxylase. Moreover, since previous studies have shown than some of these growth factors are expressed within the testis, they may play a physiological role in the regulation of differentiated testicular functions.