MODULATION OF OVINE FETAL ADRENOCORTICOTROPIN SECRETION BY ANDROSTENEDIONE AND 17-BETA-ESTRADIOL

Parturition in sheep is initiated by increases in activity of the feta l hypothalamic-pituitary-adrenal axis. We have previously reported tha t cortisol negative feedback efficacy is decreased at the end of gesta tion. The present study was designed to test the hypothesis that incre asing plasma estrogen and/or androgen concentrations in the fetus migh t increase plasma adrenocorticotropic hormone (ACTH) concentration, ei ther by stimulating ACTH secretion or by altering the negative feedbac k effect of cortisol on ACTH. Fetal sheep were chronically catheterize d and treated with no steroid (control), 17 beta-estradiol, or androst enedione (each similar to 0.24 mg/day). After catheterization and impl antation of steroid pellet, fetuses were subjected to two short (10 mi n) periods of sodium nitroprusside-induced hypotension with or without pretreatment with intravenous infusion of hydrocortisone sodium succi nate (0.5 mu g/min) to test fetal ACTH responsiveness to stress and co rtisol negative feedback efficacy. Estradiol treatment significantly i ncreased basal plasma ACTH and cortisol concentrations relative to con trol fetuses but did not interfere with the inhibition of ACTH secreti on by cortisol. Fetal plasma ACTH responses to hypotension were signif icantly suppressed similar to 60% in both control and estradiol-treate d groups. Androstenedione treatment significantly increased basal feta l plasma ACTH and decreased basal fetal plasma cortisol concentration. Androstenedione did not alter stimulated levels of fetal ACTH but did block the inhibition of stimulated ACTH by cortisol. We conclude that increased fetal cortisol and ACTH secretion at the end of gestation m ay be due to the combined effects of the gonadal steroids in that estr adiol increases basal plasma ACTH secretion while androstenedione redu ces cortisol negative feedback efficacy.