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The dynamics of 11-beta-hydroxy-androstenedione (11 OHAD) metabolism in man
Abstract:
The aim of the study was to determine the main metabolic parameters of 11-beta-hydroxy-androstenedione (11 OHAD) in man. Seven normal subjects were investigated at 1-3 months interval by 2 types of isotope dilution techniques using a tritiated tracer: constant infusion and bolus iv injection. 3H-11 OHAD and 3H-11-beta-hydroxy-androsterone (3H-11 OA) were isolated by gel column chromatography, unlabeled 11 OHAD was determined by RIA, unlabelled 11 OA by GLC. The results included computation of free and conjugated catabolite fractions. 3H-11 OHAD MCR determined from the infusion or the injection data averaged ca 1250 ml/min or 1800 L/d (CV: +/- 10%) providing a mean estimation of unlabelled 11 OHAD BPR of 1.5 +/- 0.15 mg/d. UPR estimations gave similar values. 3H-11 OHAD fractional catabolic rate drawn from the postinfusion or the injection curve averaged ca 1.4% per min (CV: +/- 7%). Mean total distribution volume ranged between 90 and 120 L according to the type of experiment. Extrapolation to time zero of the injection curve (2 exponentials) provided an estimation of 32 +/- 5 L for rapid exchange compartment. Urinary recovery of labelled compounds was complete within 24 h whereas the excretion of undegraded 3H-11 OHAD was undetectable; urinary clearance rate of 3H-conjugates approached that of creatinine. The present data show that: the secretion rate of 11 OHAD is equivalent to that of its direct precursor, adrenal androstenedione; its large MCR value results from the size of its exchange volume-equivalents.(ABSTRACT TRUNCATED AT 250 WORDS)