Decline in adrenocorticotropin receptor messenger ribonucleic acid expression in the baboon fetal adrenocortical zone in the second half of pregnancy

We have previously shown a decrease in fetal zone-specific ACTH-stimulable dehydroepiandrosterone formation and an increase in definitive zone-specific cortisol biosynthesis in the baboon fetal adrenal gland in the second half of gestation. Therefore, the fetal and definitive zones seem to develop a divergence in functional capacity with advancing gestation. We have proposed, therefore, that there is a selective decrease in ACTH receptor expression and thus tropic responsivity to ACTH within the fetal zone in the second half of primate pregnancy. The present study examined this possibility and whether corresponding changes occurred in the developmental expression of major components required for steroidogenesis. ACTH receptor messenger RNA (mRNA) levels, determined by in situ hybridization, in the fetal zone of the baboon fetal adrenal were approximately 2-fold greater (P < 0.05) at mid (i.e. day 100) than at late (i.e. day 170) gestation and 3-fold greater (P < 0.01) in the definitive zone than in the fetal zone in late gestation (term = 184 days). Both ACTH receptor and Law density lipoprotein receptor mRNA levels, determined by Northern blot in the whole fetal adrenal, also decreased (P < 0.001) by approximately 50%, whereas the mRNA levels for the definitive zone-specific Delta(5)-3 beta-hydroxysteroid dehydrogenase/isomerase (3 beta-HSD) enzyme required for cortisol biosynthesis increased over 13-fold (P < 0.001) between mid and late gestation. In contrast, mRNA expression of the steroidogenic enzymes P-450 cholesterol side-chain cleavage and 17 alpha-hydroxylase/17-20 lyase were unchanged throughout gestation. We conclude that the decrease in ACTH receptor mRNA expression and ACTH-stimulable dehydroepiandrosterone formation in the second half of gestation reflect a decline in functional capacity of the fetal zone, whereas the increase in 3 beta-HSD mRNA expression and cortisol production results from the ACTH receptor-mediated development and enhanced functional capacity of the definitive zone.