Transcriptional regulation of the lutropin/human choriogonadotropin receptor and three enzymes of steroidogenesis by growth factors in cultured pig Leydig cells.

Recent data have shown that Leydig-cell-specific functions, and therefore steroidogenic capacity, can be regulated by lutropin/human choriogonadotropin collectively termed gonadotropin and by several growth factors that are produced by and act within the testis. However, the molecular 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 beta (TGF-beta) on mRNA for the gonadotropin receptor and three steroidogenic enzymes: cytochrome P-450scc, cytochrome P-450 17 alpha-hydroxylase/C17-20 lyase (17 alpha-hydroxylase), and 3 beta-hydroxysteroid dehydrogenase. IGF-1, which can enhance testosterone production, increased gonadotropin-receptor density after an increase in receptor mRNA levels, and it increased the level of mRNA for cytochrome P-450scc 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 gonadotropin receptor density, receptor mRNA levels and the mRNA levels for 17 alpha-hydroxylase. The potential effects of these growth factors on the transcription on the gonadotropin genes for the receptor and these three steroidogenic enzymes were measured by means of nuclear run-on assays. We demonstrated that the long-term inhibitory (EGF, bFGF, TGF beta 1) or stimulatory (IGF-I) effects of these growth factors are primarily due to a variation in the transcription rates of genes for the gonadotropin receptor, cytochrome P-450scc 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.