METABOLISM OF DEHYDROEPIANDROSTERONE SULFATE (DS) IN NORMAL WOMEN AND WOMEN WITH HIGH DS CONCENTRATIONS

In order to determine the contribution of serum dehydroepiandrosterone sulfate (DS) to estrone (E1) production in normal women and the effect of chronic elevation of the serum DS concentration on DS metabolism, four normal women and four women with high endogenous serum DS were infused with [H-3]DS and [C-14]E1 or [C-14]testosterone for 6 h. Blood samples were analyzed for radioactivity as DS, dehydroepiandrosterone (D), androstenedione, testosterone, and dihydrotestosterone. Urine was collected for analysis of creatinine, 17-ketosteroids (17-KS), and radioactivity as estrone (E1). The serum DS of 12.4 +/- 1.44-mu-mol/L (mean +/- SE) in the group with high DS was higher than that of 3.96 +/- 1.0-mu-mol/L (1.46 +/- 0.37-mu-g/mL) in the normals (P < 0.005). Those with high DS also had increased 17-KS (13.2 +/- 2.0 vs. 5.68 +/- 0.68 mg/day, P < 0.025) and a higher blood production rate of DS (P(B)DS) (126 +/- 21 (n = 3) vs. 54.3 +/- 13.8 mmol/day, P < 0.05) but a lower MCR(DS) (10.94 +/- 0.61 (n = 3) vs. 13.8 +/- 0.27 L/day, P < 0.01) than that in normals. In the four normal women the fraction of infused DS converted to estrone ([rho]DS(BM) E1) was 0.00078 +/- 0.00018, the amount of E1 produced from serum DS was 41.3 +/- 15 nmol/day, the basal plasma E1 was 102 +/- 18 pmol/L, the MCR(E1) was 1340 +/- 181 L/day, the value for blood production of E1 (P(B)E1) was 129 +/- 12 nmol/day, and the portion of E1 derived from DS was 30.4 +/- 9.4%. Correlation analysis of the data from these eight subjects showed that 17-KS, P(B)DS, and the serum DS were all correlated with body surface area, body weight, and ponderal index and that 17-KS excretion, P(B)DS, and serum DS were all correlated with one another. The most important predictors of 17-KS excretion were serum DS (P < 0.001) and the ponderal index (P < 0.05).