Contribution of dehydroepiandrosterone and its sulfate to estradiol in baboon pregnancy

The metabolic clearance rates (MCR), conversion ratios (C), interconversion (rho), production rates (PR), secretion rates (SR), and relative contributions of maternal dehydroepiandrosterone (D) and D-sulfate (DS) to serum estradiol (E2) were determined in five pregnant baboons (Papio papio; 154-167 days gestation, term = 184 days) by constant intravenous infusion of [3H]DS and [14C]D. MCR-D (mean +/- SE) was greater (39.2 +/- 3.3 1/day.kg, P less than 0.001) than MCR-DS (3.1 +/- 0.3 1/day.kg). Because C-D leads to DS (5.460 +/- 0.461) exceeded (P less than 0.001) C-DS leads to (0.006 +/- 0.001), rho-DS leads to DS was greater (42.5% +/- 3.0%, P less than 0.001) than rho-DS leads to D (7.8 +/- 1.0%). C-D leads to E2 was greater (0.256 +/- 0.040) than C-DS leads to E2 (0.002 +/- 0.000). Using these values and serum levels of D (2.46 microgram/100 ml) and DS (18.9 microgram/100 ml) reported previously, SR and PR of D and DS were calculated. Of the total D produced (11.5 microgram/min), 98% was secreted, whereas only 32% of DS produced (7.1 microgram/min) was due to secretion. Using the serum D and DS levels and their conversion to E2, it was calculated that 89.7% of serum E2 was formed directly from D, 4.4% from D via DS, 1.8% from DS directly, and 4.1% from DS via D. It is concluded that, in spite of the low serum D level resulting from a high MCR, the large SR-D and more efficient conversion of D to E2 makes D, and not DS, the major circulating estrogen precursor in late baboon pregnancy.