Metabolic clearance rate (MCR) of dehydroepiandrosterone sulfate (DS), its metabolism to dehydroepiandrosterone, androstenedione, testosterone, and dihydrotestosterone, and the effect of increased plasma DS concentration on DS MCR in normal women.
The combined infusion of [3H]dehydroepiandrosterone sulfate [( 3H]DS) and [14C]estrone (E1) for 6 h in four normal women in the follicular phase of the cycle demonstrated values of 13.77 +/- 0.27 L/day (mean +/- SE) for the DS MCR (MCRDS) and 1343 +/- 206 L/day for MCRE1. The fraction of DS metabolized to dehydroepiandrosterone (D), [rho]DS-D, was 0.285 +/- 0.044, and the fraction of D arising from DS (delta D) was 0.318 +/- 0.096, determined using isotopic techniques. Raising the plasma DS concentration by 8.6 micrograms/mL (23 mumol/L) by infusing DS iv increased the MCRDS to 24.49 L/day in the first subject, and raising the plasma DS by 11.40 +/- 0.33 micrograms/mL (30.94 +/- 0.90 mumol/L) in the next three subjects raised the MCRDS to 35.7 +/- 1.3 L/day (P less than 0.01) without changing the MCRE1. The increase in MCRDS produced by increasing plasma DS makes it difficult to accurately measure the MCRDS in effect at the subject's endogenous plasma DS concentration by infusion of nonisotopic DS. Determination of the fractions of D, androstenedione (delta delta 4A), and testosterone (T) arising from DS using the increase in the plasma concentrations of these steroids produced by infusion of nonisotopic DS gave the following estimates: delta D = 0.262 +/- 0.042, delta delta 4A = 0.089 +/- 0.046, and delta T = 0.273 +/- 0.14.
Haning
R V
RV
Brown University, Providence, Rhode Island 02905.
Chabot
M
M
Flood
C A
CA
Hackett
R
R
Longcope
C
C
D000328:Adult; D000735:Androstenedione / Q000096:biosynthesis* / Q000097:blood; D003687:Dehydroepiandrosterone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000096:biosynthesis* / Q000097:blood / Q000493:pharmacokinetics; D019314:Dehydroepiandrosterone Sulfate; D013196:Dihydrotestosterone / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D004970:Estrone / Q000008:administration & dosage; D005260:Female; D005498:Follicular Phase; D006801:Humans; D008433:Mathematics; D008657:Metabolic Clearance Rate; D011863:Radioimmunoassay; D013739:Testosterone / Q000096:biosynthesis* / Q000097:blood
D013196:Dihydrotestosterone; D004970:Estrone; D013739:Testosterone; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate