The role of the pituitary gland and ACTH in the regulation of mRNAs encoding proteins essential for adrenal steroidogenesis in the late-gestation ovine fetus

To further understand the relative roles of the pituitary gland and ACTH in the regulation of mRNAs encoding proteins that are essential for adrenal d evelopment, we investigated the effects of, first, an ACTH infusion and lab our in intact fetuses and, secondly, the effect of an ACTH infusion to fetu ses with and without a pituitary gland, on the relative abundance of the mR NA encoding for the ACTH receptor (MC2R), steroidogenic factor 1 (SF-1), ch olesterol side-chain cleavage enzyme (P450(scc)), 3 beta -hydroxysteroid de hydrogenase (S beta HSD) and 17 alpha -hydroxylase (P450(C17)) in the fetal adrenal gland. ACTH(1-24) infusion (14.7 pmol/kg per h) to intact fetuses was without effect on the abundance of mRNA encoding MC2R and SF-1, irrespe ctive of whether the infusion was given for 18 (115-132 days of gestation) or 32 days (115 days to term (147 days of gestation)). Hypophysectomy (HX) did not alter the expression of MC2R mRNA; however, the abundance of SF-1 m RNA fell by approximately 50% following the removal of the pituitary gland. ACTH(1-24) infusion to HX fetuses failed to restore levels of SF-1 mRNA to that seen in intact animals. P450(scc) and 3 beta HSD mRNAs were increased by ACTH(1-24) infusion for 18 days in. intact animals, although no effects of the infusion were seen on P450(C17) mRNA levels. For all three of these mRNAs, there was a significant increase in their abundance between 132 day s of gestation and term in intact fetuses. By term, ACTH(1-24) infusion was without any additional effect on their abundance. HX decreased the express ion of P450(scc), 3 beta HSD and P450(C17) mRNAs, while ACTH(1-24) infusion to HX fetuses increased the expression of these mRNAs to levels seen in in tact animals. There were significant correlations between the abundance of the mRNA for P450(scc), 3 beta HSD and P450(C17), but not MC2R and SF-1, an d premortem plasma cortisol concentrations. These results emphasise the imp ortance of the pituitary gland and ACTH in the regulation of the enzymes in volved in adrenal steroidogenesis. Factors in addition to ACTH may also pla y some role, as the infusion was not always effective in increasing the abu ndance of the mRNAs. Surprisingly, the mRNA for MC2R and SF-1 did not appea r to be regulated by ACTH in the late-gestation ovine fetus, though a pitui tary-dependent factor may be involved in the regulation of SF-1 mRNA abunda nce.