DIVERGENT CHANGES IN PLASMA ACTH AND PITUITARY POMC MESSENGER-RNA AFTER CORTISOL ADMINISTRATION TO LATE-GESTATION OVINE FETUS

Plasma concentrations of cortisol and adrenocorticotropic hormone (ACT H) rise in the late-gestation sheep fetus at approximately the same ti me as there is an increase in the plasma levels of corticosteroid-bind ing globulin (CBG). We hypothesized that intrafetal cortisol infusion during late pregnancy would stimulate an increase in fetal plasma CBG, which in turn would bind cortisol and diminish glucocorticoid negativ e-feedback regulation of the fetal pituitary, leading to an increase i n plasma ACTH concentrations. Cortisol was infused into chronically ca theterized fetal sheep beginning at 126.1 +/- 0.5 days of gestation an d continued for 96 h. Control fetuses were infused with saline. In cor tisol-infused fetuses, the plasma cortisol concentrations rose signifi cantly from control levels (4.4 +/- 0.6 ng/ml) to 19.3 +/- 3.1 ng/ml w ithin 24 h and remained significantly elevated throughout the infusion period. Plasma immunoreactive (ir) ACTH concentrations were significa ntly elevated in cortisol-infused fetuses within 24-48 h and remained significantly higher than in controls throughout the 96-h experimental period. Plasma free cortisol concentrations increased 10-fold and rem ained significantly elevated in cortisol-infused animals, despite a ri se in plasma corticosteroid-binding capacity. Levels of pituitary proo piomelanocortin (POMC) mRNA in the fetal pars distalis and pars interm edia were 96 and 38% lower, respectively, after 96 h of cortisol infus ion. Therefore physiological elevations of plasma cortisol, in the lat e-gestation ovine fetus, lead to increases in mean plasma irACTH conce ntrations, but this is not associated with increases in fetal pituitar y POMC mRNA levels.