Development of fetal pituitary-adrenal function.

The factors responsible for the growth of the fetal adrenal, and its increase in cortisol secretion during late pregnancy have been examined in experimental studies in sheep. The fetal pituitary is necessary for these changes to occur. However, the increase in cortisol secretion at term is not preceded by an increase in ACTH in fetal plasma. Prolactin increases in parallel with fetal cortisol. ACTH is elevated in fetal plasma during late pregnancy, despite the demonstration of a negative feedback relationship with cortisol, suggesting an overriding stimulus to ACTH. Comparison of fetal ACTH levels during Synacthen (β1–24 ACTH) infusion into intact and hypophysectomized fetal lambs demonstrates endogenous ACTH release at this time. The possible mechanisms by which negative feedback may be overridden are discussed.Studies in vivo and in vitro show that there is a maturation of fetal adrenal sensitivity during late pregnancy. In vivo at days 120–130, ACTH provokes little or no increase in the fetal adrenal secretion of cortisol, whereas intra-fetal infusion of prostaglandin E₂, but not PGF_2α, provokes a rapid 300% increase in the cortisol concentration in fetal plasma. These findings indicate that the fetal adrenal has the pathway necessary for cortisol production by day 130 p.c., and suggest that adrenal maturation is a key factor in the release of cortisol which precedes parturition.