Estrogen Metabolism in the Human. I. Studies in the Male Using Estrone-6,7-3H, with Special Reference to Estrone Production Rate Determinations, the Origin of Certain Urinary Estrogen Conjugates, and the Use of a New Mathematical Model

Abstract

Estrone-6,7-³H was administered to a group of 12 normal males. The mean urinary excretion of conjugated estrone, estradiol-17β and estriol estimated following acid hydrolysis was (% of administered radioactivity, sd in parentheses): 9.9 (2.4), 1.05 (0.52) and 10.4 (4.1), respectively. The mean daily excretion of the corresponding endogenous (nonradioactive) estrogen conjugates was (μg/day, SD in parentheses): 4.40 (0.88), 0.82 (0.35) and 3.85 (2.06). Corresponding unconjugated estrogens were present only in insignificant amounts. Mean estrone production rate, calculated from the specific activity of conjugated urinary estrone estimated after acid hydrolysis, was 46.3 μg/day, SD 12.7. The mean specific activity of conjugated estrone estimated with glucuronidase hydrolysis was not significantly different from that estimated with acid hydrolysis, suggesting that both moieties represent “exclusive” metabolites of estrone. The mean specific activities of conjugated estrone, estradiol-17β and estriol using acid hydrolysis were significantly different. A mathematical model in the form of a regression equation was developed and used to relate the radioactive and nonradioactive data in order to gain information regarding the origin of urinary estrone, estradiol-17β and estriol conjugates. Analysis of the model yielded results consistent with the hypothesis that conjugates of these 3 urinary estrogens are derived solely from estrone secreted into an inner pool which includes plasma, a conclusion different from that which might be arrived at from consideration of the specific activities alone.