The peptide ACTH(1-39), adrenal growth and steroidogenesis in the sheep fetus after disconnection of the hypothalamus and pituitary

1. We have investigated the role of the fetal hypothalamo-pituitary axis in the control of adrenocortical growth and steroidogenesis in the sheep fetus during late gestation. Plasma concentrations of ACTH(1-39) increased between 120-125 and 136-142 days (P < 0.05), but did not change after surgical disconnection of the fetal hypothalamus and pituitary (HPD) at 106-120 days gestation. There was no effect of either gestational age or HPD on the circulating concentrations of the ACTH-containing precursors pro-opiomelanocortin (POMC) and pro-ACTH (the 22 kDa N-terminal portion of POMC). 2. In the fetal sheep adrenal, the relative abundance of the mRNAs of the steroidogenic enzymes CYPIIA1 and CYP21A1 increased between 130-135 and 136-140 days gestation (P < 0.05) and remained high after 141 days, whereas that of CYP17 mRNA increased after 141 days gestation (P < 0.05). The abundance of adrenal 3 beta-HSD mRNA did not change between 130 and 145 days. 3. Hypothalamo-pituitary disconnection significantly reduced the abundance of of CYPIIA1 mRNA, 3 beta-HSD mRNA and CYP17 mRNA by 3.4, 3.1 and 3.7 times, respectively, at 140-142 days gestation (P < 0.05). 4. In the intact group of fetal sheep, adrenal weight increased between 130-135 and 141-145 days (P < 0.05), but there was no change in the abundance of adrenal insulin-like growth factor II (IGF-II) mRNA across this gestational age range. Hypothalamo-pituitary disconnection significantly reduced fetal adrenal weight to 66% that of intact sheep (P < 0.01), but did not alter the abundance of IGF-II mRNA in the fetal adrenal at 140-142 days. 5. Our results suggest that the prepartum changes in adrenal growth and steroidogenesis are under the control of an intact hypothalamo-pituitary axis in late gestation and are dependent on an increase in circulating ACTH(1-39), rather than on ACTH precursors. We have found no evidence, however, for a direct-relationship between fetal adrenal growth or steroidogenesis and adrenal IGF-II mRNA between 130 and 145 days gestation.