Transcriptional Regulation of the Lutropin/Human Choriogonadotropin Receptor and Three Enzymes of Steroidogenesis by Growth Factors in Cultured Pig Leydig Cells

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Abstract
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 β (TGF-β) on mRNA for the gonadotropin receptor and three steroidogenic enzymes: cytochrome P-450SCC, cytochrome P-450 17α-hydroxylase/C17–20 lyase (17α-hydroxylase), and 3β-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 17α-hydrolyase. Micromolar concentrations of insulin had similar effects to those of IGF-I. Moreover, the three factors that decreased testosterone production (EGF, bFGF and TGFβ1) decreased gonadotropin receptor density, receptor mRNA levels and the mRNA levels for 17α-hydroxylase. The potential effects of these growth factors on the transcription of the gonadotropin genes for the receptor and these three steroidogenic enzymes were measured by means of nuclear run-on assays. We demonstated that the long-term inhibitory (EGF, bFGF, TGFβ1) 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 17α-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.

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