Developmental and hormonal regulation of mRNAs for insulin-like growth factor II and steroidogenic enzymes in human fetal adrenals and gonads.

Insulin-like growth factor II (IGF-II) is regulated developmentally and hormonally in human fetal gonads and adrenals. The abundance of IGF-II mRNA is greatest in RNA from human fetal adrenals, followed by fetal liver, testis, placenta, and ovaries. Fetal testicular IGF-II mRNA decreases significantly with increasing gestational age, in parallel with our previous measurements of the mRNAs for the steroidogenic enzymes P450scc (cholesterol side-chain cleavage enzyme) and P450c17 (17 alpha-hydroxylase/17,20 lyase) (J. Clin. Endocrinol. Metab. 63, 1145, 1986). The abundances of P450scc and P450c17 mRNAs in cultured fetal testis cells rose 2.5-fold (p less than 0.01) and 9.2-fold (p less than 0.001), respectively, in response to 0.5 mM cAMP, but the abundance of IGF-II mRNA was not affected. This suggests that the IGF-II gene is regulated differently in fetal testes than it is in fetal adrenals, placenta, or adult granulosa cells, where we have previously shown that ACTH, cAMP, and gonadotropins, respectively, increase IGF-II mRNA accumulation (Proc. Natl. Acad. Sci. USA 84, 1590, 1987). Exogenously added IGF-I and IGF-II had no effect on mRNAs for P450c17 or P450c21 (21-hydroxylase), but decreased IGF-II mRNA in ACTH-stimulated fetal adrenal cells. Thus, the IGFs appear to exert short-loop feedback inhibition on accumulation of IGF-II mRNA.