Differential Actions of Metyrapone on the Fetal Pituitary-Adrenal Axis in the Sheep Fetus in Late Gestation1

It is not clear if an increase in intra-adrenal cortisol is re-quired to mediate the actions of adrenocorticotropic hormone (ACTH) on adrenal growth and steroidogenesis during the pre-partum stimulation of the fetal pituitary-adrenal axis. We infused metyrapone, a competitive inhibitor of cortisol biosynthesis, into fetal sheep between 125 and 140 days of gestation (term 5 147 6 3 days) and measured fetal plasma cortisol, 11-desox-ycortisol, and ACTH; pituitary pro-opiomelanocortin mRNA and adrenal expression of ACTH receptor (melanocortin type 2 re-ceptor), steroidogenic acute regulatory protein (StAR), 11b-hy-droxysteroid dehydrogenase type 2 (11bHSD2), cytochrome P450 cholesterol side-chain cleavage (CYP11A1), cytochrome P450 17-hydroxylase (CYP17), 3b-hydroxysteroid dehydroge-nase, and cytochrome P450 21-hydroxylase mRNA; and StA