SUPPRESSION OF MATERNAL ADRENAL DEHYDROEPIANDROSTERONE AND DEHYDROEPIANDROSTERONE-SULFATE PRODUCTION BY ESTROGEN DURING BABOON PREGNANCY

We have recently demonstrated that estrogen reduced the responsivity o f the baboon fetal adrenal gland to ACTH with respect to the formation of dehydroepiandrosterone (DKA) and therefore have proposed that a re gulatory system exists for feedback control of estrogen on fetal adren al androgen production. Because the maternal adrenal also provides DHA and DHA sulfate (DHAS) for placental estrogen synthesis, we determine d whether an estrogen-androgen feedback system is operative in the mat ernal-placental unit. Serum DHA/DHAS and cortisol concentrations were determined by RIA in maternal blood samples obtained at 1- to a-day in tervals from intact baboons untreated (n=4) or treated sc with estradi ol 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 DH A and DHAS were eliminated by fetectomy on day 100 (n=4); and from fet ectomized baboons treated with estradiol on day 130 to term (n=3). Mat ernal serum DKA and DHAS levels increased (P<0.001) in controls betwee n day 80 and term to means +/-SE of 46.8+/-2.4 nmol/L and 0.507+/-0.04 8 mu mol/L, respectively, on days 150-184. Estrogen increased serum es tradiol 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 mu mol/L, r espectively, on days 150 to 184. After fetectomy, serum estradiol decr eased 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 incre ased mean maternal serum estradiol concentration to 12.15+/-0.37 nmol/ L and reduced (P<0.01) DKA and DHAS to 11.9+/-0.7 nmol/L and 0.102+/-0 .005 mu mol/L. In contrast, serum cortisol levels were not altered in baboons by estrogen treatment. The estrogen-induced decrease in matern al DHA/DHAS levels reflected a decline in adrenal production; the MCRs (liters/day) of DHA and DHAS in three nonpregnant baboons were simila r 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 thes e results and our previous observations in fetal baboons, we propose t hat a negative feedback system exists in utero whereby placental produ ct estrogen regulates maternal and fetal adrenal C-19-steroid producti on to maintain a physiologically normal balance of estrogen biosynthes is during primate pregnancy.