Effects of cortisol and estradiol on pituitary expression of proopiomelanocortin, prohormone convertase-1, prohormone convertase-2, and glucocorticoid receptor mRNA in fetal sheep

We hypothesized that in the late-gestation sheep fetus there is an interact ion between the prepartum rise in cortisol and the increase in placental es tradiol production that allows expression of key components of the fetal hy pothalamic-pituitary-adrenal (HPA) axis. Therefore, the goal of this study was to investigate the effects of cortisol on the fetal HPA axis in the pre sence and absence of increased placental estradiol production. We obtained fetal plasma samples and pituitary tissue from animals that had received an infusion of either cortisol, cortisol and 4-hydroxyandrostenedione (4OHA, an aromatase inhibitor), saline, or saline + 4OHA controls. Cortisol signif icantly decreased plasma adrenocorticotropic hormone concentrations, and in the presence of 4OHA reduced pituitary proopiomelanocortin (POMC) mRNA lev els in the pars distalis. There was no effect of any treatment on the expre ssion of the key POMC processing enzymes, prohormone convertase-1 or -2 in the fetal pituitary. Conversely, levels of glucocorticoid receptor (GR) mRN A in the pituitary were increased with cortisol treatment in the absence of increased estradiol. We suggest that in the late-gestation sheep fetus, co rtisol and estradiol have opposite effects on pituitary POMC and GR mRNA ex pression, and interact to regulate these key components of the fetal HPA ax is.