DIFFERENTIAL REGULATION OF PROOPIOMELANOCORTIN MESSENGER-RIBONUCLEIC-ACID IN THE PARS-DISTALIS AND PARS-INTERMEDIA OF THE PITUITARY-GLAND AFTER PROLONGED HYPOXEMIA IN FETAL SHEEP

POMC messenger RNA (mRNA) is synthesized and translated to form ACTH i n the pars distalis and ACTH-related peptides in the pars intermedia o f the pituitary in fetuses of species such as sheep. In the fetal shee p, maturation of hypothalamo-pituitary-adrenal (HPA) function occurs d uring late pregnancy accompanied by increased levels of POMC mRNA in t he pars distalis, and contributes to the stimulus far birth. Activatio n of fetal HPA function also occurs with short term hypoxemia. However , the effects of more prolonged fetal hyperemia, which may predispose to premature parturition, on POMC mRNA levels in the pars distalis and pars intermedia are not known. We studied the effects of sustained hy poxemia (48 h) in the absence of acidosis on fetal HPA responses at tw o times in late gestation, days 126-130 and days 134-136 (term = simil ar to 145 days). Hypoxemia was induced by lowering the fraction of oxy gen in the maternal inspired gas mixture. Fetal arterial oxygen tensio n fell by 6-8 mm Hg, without a change in fetal arterial pH or carbon d ioxide tension. Pituitary POMC mRNA was localized and quantified by in situ hybridization. At both gestational ages, hypoxemia caused a tran sient elevation in fetal plasma ACTH, with a maximum response at +2 h, and a sustained elevation in circulating cortisol. Cortisol responses were greater in the older fetuses. Changes in plasma cortisol were no t associated with alterations in the plasma corticosteroid-binding cap acity or in levels of hepatic corticosteroid-binding globulin mRNA. Pi tuitary POMC mRNA showed a regional distribution in the pars distalis, and mean levels increased with gestational age. After 48 h of hypoxem ia, POMC mRNA levels had increased in the pars distalis. The regional distribution was unaffected by the hypoxemic insult. In contrast, POMC mRNA levels in the pars intermedia decreased after hypoxemia, and the reduction was greater in the older fetuses. We conclude that in respo nse to prolonged hypoxemia, there is differential regulation of POMC m RNA levels in the pars distalis and pars intermedia of the pituitary i n fetal sheep. The magnitude of these responses also changes with gest ational age. The increase in POMC mRNA levels in the pars distalis at 48 h of hypoxemia, despite a rise in plasma cortisol and without a cha nge in corticosteroid-binding globulin, suggests altered regulation of HPA function at this time.