Relationship of uteroplacental blood flow to the placental clearance of maternal dehydroepiandrosterone through estradiol formation in the pregnant baboon.
The theory that maternal intervillous blood flow is a major determinant of the rate at which the placenta clears androgenic steroid precursors through estrogen formation has never been tested by direct experimentation. We studied the effects of graded reductions in maternal distal aortic blood flow (Qda) on the placental clearance (PC) of dehydroepiandrosterone (D) through estradiol (E2) formation in pregnant baboons near term. A continuous iv infusion of [7-3H]D and [4-14C]E2 was administered to four pregnant baboons (Papio anubis) at 155-165 days gestation (term, 184 days) for 270 min (t0-t270). Maternal Qda was continuously recorded by electromagnetic flow transducer at the aortic bifurcation and altered with an aortic snare device. A 50% reduction in Qda was imposed at t60 and released at t180. Blood samples were collected at 10-min intervals from t30-t60 (control interval), t120-t180 (occlusion interval), and t240-t270 (release interval). All four animals were later studied after pregnancy with an identical infusion for 90 min, with blood samples obtained at 10-min intervals from t30-t90. Equilibrium concentrations of [3H]D, [3H]E2, and [14C]E2 in plasma were determined and the MCR of D (MCR-D), the transfer constant of conversion of D to E2 (rho DE2), and the PC of D through E2 formation (PCDE2) were calculated for each of the three levels of Qda corresponding to the control, occlusion, and release intervals in pregnant animals and under conditions of existing Qda in the nonpregnant state. Control MCR-D during pregnancy (mean +/- SE, 740 +/- 74 liters/day) exceeded MCR-D after pregnancy (500 +/- 40 liters/day). MCR-D fell significantly during occlusion (P less than 0.05). Both rho DE2 and PCDE2 decreased uniformly when Qda was reduced by 50% and returned toward the control level with release of the aortic constriction. The mean rho DE2 in pregnant animals was 0.068 +/- 0.0073 (+/- SE), 0.039 +/- 0.0020, and 0.059 +/- 0.0063 during control, occlusion, and release intervals, respectively, all exceeding rho DE2 in the nonpregnant state (0.013 +/- 0.0004). Control mean PCDE2 was 46.3 +/- 8.24 (+/- SE) ml/min; it decreased to 18.9 +/- 2.68 with 50% reduction in Qda and was 35.6 +/- 5.43 when Qda was restored to 75% of the control value. PCDE2 was directly proportional to Qda (r2 = 0.98; P less than 0.01; n = 12) and remained a constant fraction (0.13 +/- 0.002) thereof in all four animals.(ABSTRACT TRUNCATED AT 400 WORDS)