HYPOTHALAMOPITUITARY DISCONNECTION OF THE LATE-GESTATION OVINE FETUS RESULTS IN PROFOUND CHANGES IN CORTISOL SECRETION THAT ARE NOT REFLECTED IN COMMENSURATE CHANGES IN ADRENOCORTICOTROPIN SECRETION

A prepartum increase in fetal glucocorticoid concentrations is essenti al for the perinatal transition to extrauterine life for many mammalia n species. In the case of the sheep, this increase in cortisol is also the trigger for parturition, and depends upon an intact hypothalamopi tuitary unit. Fetal sheep that have undergone hypothalamo-pituitary di sconnection (HPD) fail to have a prepartum cortisol surge or initiate labor, despite apparently normal fetal ACTH concentrations in late ges tation. We have investigated whether a defect exists in the regulation of pulsatile neurohormone secretion in the pituitary-adrenal axis of the HPD sheep fetus, by comparing immunoreactive (ir) ACTH and cortiso l secretory dynamics in intact and HPD fetuses at 126 and 145 days of gestation (normal gestation length, 147 days). The fetal surgery was c onducted at 115 days of gestation. Blood samples were collected at 5-m in intervals for 2 h on each experimental day, and the resulting irACT H and cortisol concentrations were analyzed by multiple-parameter deco nvolution and cross-correlation analysis. Basal irACTH secretion was l ess (P < 0.01) in HPD fetuses than intact fetuses at 126 days, but it had recovered by 145 days. There were no differences in irACTII half-l ife or the number or duration of irACTH secretory bursts between the t wo groups of fetuses or the two gestational ages (GAs). The size of th e irACTH secretory bursts was not affected by the operation, but it in creased with GA to a similar extent in both groups of fetuses (P < 0.0 1). In keeping with the observations for irACTH secretion, there was n o effect of age or the operation on cortisol half-life or on the numbe r or duration of cortisol secretory bursts. In contrast, there were dr amatic age-related increases (P < 0.01) in the basal cortisol secretio n rate and the size of the cortisol secretory bursts in the intact, bu t not the HPD, fetuses. Cross-correlation analysis revealed a signific ant (P < 0.01) concordance between irACTH and cortisol secretion in on ly the intact fetuses at 126 days; this was not apparent in the intact fetuses at 145 days, or in the young or old HPD fetuses. These findin gs confirm a major defect in cortisol secretion in the late-gestation HPD fetus but suggest that this is not caused by defects in irACTH sec retion. Together with other observations, these data suggest that ACTH may not be the sole, or primary, regulator of adrenal cortisol secret ion in the late-gestation ovine fetus.