REGULATION OF CORTICOTROPIN AND STEROIDOGENIC ENZYME MESSENGER-RNAS IN HUMAN FETAL ADRENAL-CELLS BY CORTICOTROPIN, ANGIOTENSIN-II AND TRANSFORMING GROWTH-FACTOR BETA(1)

Using cultured human fetal adrenal cells, we have investigated the basal secretion of cortisol and dehydroepiandrosterone sulfate (DHAS) and the effect of corticotropin (ACTH), angiotensin-II (A-II) and transforming growth factor beta(1) (TGF beta(1)) on the secretion of these steroids and on the mRNA levels of ACTH receptor (ACTH(R)), cytochrome P450scc (cholesterol side-chain cleavage), P450 17 alpha (17 alpha-hydroxylase/l7-20 lyase) and 3 beta-HSD (3 beta-hydroxysteroid dehydrogenase). The basal DHAS/cortisol ratio declined progressively between 12.5 and 21 weeks. ACTH treatment enhanced the secretion of cortisol and to a lesser extent that of DHAS, and increased the steroidogenic response to an acute stimulation with ACTH. These changes were associated with increased mRNA levels of ACTH(R) and of the steroidogenic enzymes. A-II treatment also increased the secretion of both DHAS and cortisol, but less than ACTH, enhanced the responsiveness to ACTH and increased ACTH(R), P450scc and P450 17 alpha mRNA levels. In contrast, TGF beta(1) alone or together with ACTH decreased DHAS secretion, but not cortisol secretion. Moreover, TGF beta(1) had no effect on ACTH(R) and P450scc mRNA levels, decreased by about 50% the mRNA levels of P450 17 alpha both in the absence or presence of ACTH, but enhanced the stimulatory effects of ACTH on 3 beta-HSD mRNA. These results, along with those previously reported, suggest that both A-II and TGF beta may play a role in fetal adrenal function. In addition, they show that the effects of both peptides are qualitatively different from, even sometimes opposite to, those previously reported in bovine and ovine adrenal cells.