I. R. Young

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.