Metabolic clearance rate of dehydroepiandrosterone sulfate, its metabolism to testosterone, and its intrafollicular metabolism to dehydroepiandrosterone, androstenedione, testosterone, and dihydrotestosterone in vivo.
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.
Haning
R V
RV
Brown University, Providence, Rhode Island.
Flood
C A
CA
Hackett
R J
RJ
Loughlin
J S
JS
McClure
N
N
Longcope
C
C
D000328:Adult; D000735:Androstenedione / Q000378:metabolism*; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000493:pharmacokinetics; D019314:Dehydroepiandrosterone Sulfate; D005260:Female; D006801:Humans; D008657:Metabolic Clearance Rate; D010053:Ovary / Q000378:metabolism*; D011863:Radioimmunoassay; D013739:Testosterone / Q000031:analogs & derivatives* / Q000378:metabolism*
D013739:Testosterone; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; C013915:boldenone