DECLINE IN ADRENOCORTICOTROPIN RECEPTOR MESSENGER-RIBONUCLEIC-ACID EXPRESSION IN THE BABOON FETAL ADRENOCORTICAL ZONE IN THE 2ND HALF OF PREGNANCY

We have previously shown a decrease in fetal zone-specific ACTH-stimul able dehydroepiandrosterone formation and an increase in definitive zo ne-specific cortisol biosynthesis in the baboon fetal adrenal gland in the second half of gestation. Therefore, the fetal and definitive zon es seem to develop a divergence in functional capacity with advancing gestation. We have proposed, therefore, that there is a selective decr ease in ACTH receptor expression and thus tropic responsivity to ACTH within the fetal zone in the second half of primate pregnancy. The pre sent 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, deter mined 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 < 0.0 1) in the definitive zone than in the fetal zone in late gestation (te rm = 184 days). Both ACTH receptor and Law density lipoprotein recepto r mRNA levels, determined by Northern blot in the whole fetal adrenal, also decreased (P < 0.001) by approximately 50%, whereas the mRNA lev els for the definitive zone-specific Delta(5)-3 beta-hydroxysteroid de hydrogenase/isomerase (3 beta-HSD) enzyme required for cortisol biosyn thesis increased over 13-fold (P < 0.001) between mid and late gestati on. In contrast, mRNA expression of the steroidogenic enzymes P-450 ch olesterol side-chain cleavage and 17 alpha-hydroxylase/17-20 lyase wer e unchanged throughout gestation. We conclude that the decrease in ACT H receptor mRNA expression and ACTH-stimulable dehydroepiandrosterone formation in the second half of gestation reflect a decline in functio nal capacity of the fetal zone, whereas the increase in 3 beta-HSD mRN A expression and cortisol production results from the ACTH receptor-me diated development and enhanced functional capacity of the definitive zone.