At the time of surgery, women were infused with [3H]dehydroepiandrosterone sulfate ([3H]DS)/[14C]testosterone ([14C]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 4A). 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 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 MCRDS, 607 +/- 90 L/day (n = 3) for MCRT, and 0.0190 +/- 0.0089 (n = 3) for [p]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 3H-labeled and three [14C-labeled metabolites: [3H]D (21-fold; P less than 0.001), [3H]T (81-fold; P less than 0.001), [3H]DHT (19-fold; P less than 0.001), [14C]T (4-fold; P less than 0.025), [14C]DHT (21-fold; P less than 0.01), and [14C]delta 4A (50-fold; P less than 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 4 A, 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.
Evidence has suggested that dehydroepiandrosterone sulfate (DS) is a prehormone for ovarian steroidogenesis. To study this hypothesis, combined 6-h infusions of [3H]dehydroepiandrosterone sulfate and [14C]testosterone ([14C]T) were performed in four normal women treated with menotropins who were undergoing medically indicated surgery, and the data were compared to those from nine normal women. The concentrations of tracer and nonisotopic DS, androst-5-ene-3 beta,17 beta-diol sulfate (delta 5diolS), androst-5-ene-3 beta,17 beta-diol (delta 5diol), dehydroepiandrosterone (D), androstenedione (delta 4A), and T were determined in arterial and venous blood and in follicular fluid. From these data, the concentrations and fractions of steroids in the follicular fluid that were derived from DS were calculated from the specific activity of intravascular DS and the concentrations of follicular fluid tracer steroids and their specific activities. The fractions of T (0.48), delta 5diol (0.31), delta 5diolS (0.42), and D (0.25) in follicular fluid arising from circulating DS were similar and were not significantly different from that of follicular DS arising from circulating DS (0.32). However, the fraction of follicular fluid delta 4A (0.041) was significantly less (P < 0.01), and the fractions of intrafollicular estrone and estradiol arising from DS were both less than 0.04. The mean MCR of DS in the women treated with menotropins of 22.0 +/- 3.5 L/day (mean +/- SE) was significantly higher than the normal control value. These findings elucidate an important mechanism of adrenal/ovarian interaction at the level of steroidogenesis; circulating DS serves as a prehormone for the production of intrafollicular delta 5diolS, delta 5 diol, D, and T.
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