EFFECTS OF LONG-TERM HYPOXEMIA ON PITUITARY-ADRENAL-FUNCTION IN FETALSHEEP

To test the hypothesis that long-term hypoxemia causes premature activ ation of the fetal pituitary-adrenal function, we embolized the fetal side of the placenta in pregnant sheep and examined the changes in con centrations of immunoreactive adrenocorticotropic hormone (irACTH), co rtisol, and prostaglandin E(2) (PGE(2)) in fetal plasma, and levels an d localization of proopiomelanocortin (POMC) mRNA in the pars distalis and the pars intermedia of the fetal pituitary. Twelve fetal sheep we re studied (6 embolized and 6 control) for 21 days between 0.74 and 0. 88 of gestation. Daily injections of nonradiolabeled microspheres were given into the fetal abdominal aorta to decrease fetal arterial oxyge n content by 40-50% of the preembolization values. In the embolized gr oup, concentrations of irACTH, PGE(2), and cortisol in fetal plasma in creased gradually and were significantly (P <0.05) elevated above thos e of controls after day 20, day 16, and day 20, respectively. POMC mRN A levels in the pars distalis of the fetal pituitary were not differen t from those of controls but were significantly reduced in the pars in termedia (P <0.05). We conclude that levels of POMC mRNA in the pars d istalis are unchanged during long-term hypoxemia possibly because of n egative feedback effects of elevated cortisol on the pituitary gland. During long-term fetal hypoxemia, there is a differential regulation o f POMC mRNA expression in the pars distalis and pars intermedia.