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Influence of Estradiol and Androstenedione on ACTH and Cortisol Secretion in the Ovine Fetus

Objective: To test the hypothesis that physiologic increases in fetal plasma 17β-estradiol and androstenedione modulate the activity of the fetal hypothalamic-pituitary-adrenal (HPA) axis. Methods: Seventeen pregnant ewes and their fetuses were chronically catherized. At the time of surgery, the fetuses received implants that released 17β-estradiol (n = 5) alone or 17β-estradiol and androstenedione (n = 6), each at a rate of approximately 250 μg/day for each steroid. The control group (n = 6) received either no pellet (n = 2) or a “placebo” pellet, which contained no steroid (n = 4). Fetal blood samples were drawn for hormone and blood gas analysis at 1-3-day intervals until the time of spontaneous parturition. Fetal plasma ACTH and cortisol concentrations were fit to semilogarithmic equations and analyzed by stepwise multiple linear regression analysis for statistically significant effects of 17β-estradiol and androstenedione. Results: Estradiol significantly increased and androstenedione significantly decreased the ACTH and cortisol concentrations. Treatment with both 17β-estradiol and androstenedione resulted in parturition approximately 4 days earlier than in the other groups (P < .05). Conclusions: Physiologic increases in fetal plasma estradiol and androstenedione modify the activity of the HPA axis.