METABOLIC-CLEARANCE RATE OF DEHYDROEPIANDROSTERONE SULFATE, ITS METABOLISM TO TESTOSTERONE, AND ITS INTRAFOLLICULAR METABOLISM TO DEHYDROEPIANDROSTERONE, ANDROSTENEDIONE, TESTOSTERONE, AND DIHYDROTESTOSTERONE INVIVO

At the time of surgery, women were infused with [H-3]dehydoepiandrosterone sulfate ([H-3]DS)/[C-14]testosterone ([C-14]T) for 6 h; blood samples were obtained from an artery, the ovarian veins, and a peripheral vein; and fluid was obtained from ovarian follicles. Both blood and follicular fluid samples were analyzed for radioactivity as DS, dehydroepiandrosterone (D), androstenedione (DELTA-4-A), T, and dihydrotestosterone (DHT), and the blood was also analyzed for the concentration of nonisotopic DS by RIA. In other subjects the concentrations of D and DS by RIA. In other subjects the concentrations of D and DS were measured in paired samples of blood and follicular fluid. From these data, values of 13.6 +/- 0.69 L/day four (mean +/- SE; n = 4) for MCR(DS), 607 +/- 90 L/day (n = 3) for MCR(T), and 0.0190 +/- 0.0089 (n = 3) for [rho]DS-T (fraction of plasma DS metabolized to plasma T) were obtained. The ratio of the concentration of the tracer-labeled steroid in the follicular fluid to the concentration in the arterial plasma sample was elevated significantly above 1 for three H-3-labeled and three [C-14-labeled metabolites: [H-3]D (21-fold; P < 0.001), [H-3]T (81-fold; P < 0.001), [H-3]DHT (19-fold; P < 0.001), [C-14]T (4-fold; P < 0.025), [C-14]DHT (21-fold; P < 0.01), and [C-14]DELTA-4A (50-fold; P < 0.001). The estimated concentrations of steroids in follicular fluid derived from DS based on specific activity calculations were as follows: [geometric mean (95% confidence limits; n)]: DS, 5600 (4800-6500 nmol/L; 12); D, 370 (88-1500 nmol/L; 10); DELTA-4A, 120 (67-220 nmol/L; 12); T, 130 (39-450 nmol/L; 10); and DHT, 64 (35-120 nmol/L; 8). Comparison of these data to known follicular fluid steroid concentrations shows that DS from the intravascular pool can be used as an ovarian prehormone.