We have recently demonstrated that estrogen reduced the responsivity of the baboon fetal adrenal gland to ACTH with respect to the formation of dehydroepiandrosterone (DHA) and therefore have proposed that a regulatory system exists for feedback control of estrogen on fetal adrenal androgen production. Because the maternal adrenal also provides DHA and DHA sulfate (DHAS) for placental estrogen synthesis, we determined whether an estrogen-androgen feedback system is operative in the maternal-placental unit. Serum DHA/DHAS and cortisol concentrations were determined by RIA in maternal blood samples obtained at 1- to 2-day intervals from intact baboons untreated (n = 4) or treated sc with estradiol benzoate (n = 3, beginning with 1 mg/day and increasing by 1 mg each day) on days 150 to 184 (term); from animals in which fetal adrenal DHA and DHAS were eliminated by fetectomy on day 100 (n = 4); and from fetectomized baboons treated with estradiol on day 130 to term (n = 3). Maternal serum DHA and DHAS levels increased (P < 0.001) in controls between day 80 and term to means +/- SE of 46.8 +/- 2.4 nmol/L and 0.507 +/- 0.048 mumol/L, respectively, on days 150-184. Estrogen increased serum estradiol concentrations by 78% to 14.50 +/- 0.84 nmol/L and decreased (P < 0.001) DHA and DHAS to 17.2 +/- 1.3 nmol/L and 0.246 +/- 0.015 mumol/L, respectively, on days 150 to 184. After fetectomy, serum estradiol decreased to a level that was 5% of controls, and maternal DHA increased (P < 0.01) to 75.2 +/- 4.8 nmol/L. Estrogen treatment after fetectomy increased mean maternal serum estradiol concentration to 12.15 +/- 0.37 nmol/L and reduced (P < 0.01) DHA and DHAS to 11.9 +/- 0.7 nmol/L and 0.102 +/- 0.005 mumol/L. In contrast, serum cortisol levels were not altered in baboons by estrogen treatment. The estrogen-induced decrease in maternal DHA/DHAS levels reflected a decline in adrenal production; the MCRs (liters/day) of DHA and DHAS in three nonpregnant baboons were similar before (414 +/- 119 and 29.3 +/- 5.6, respectively) and after (359 +/- 66 and 30.4 +/- 3.4, respectively) estradiol treatment, which decreased (P < 0.05) serum DHA and DHAS levels by more than 90%. On the basis of these results and our previous observations in fetal baboons, we propose that a negative feedback system exists in utero whereby placental product estrogen regulates maternal and fetal adrenal C19-steroid production to maintain a physiologically normal balance of estrogen biosynthesis during primate pregnancy.
