Evidence for a Two-Pool System Governing the Excretion of Radioactive Urinary Estrogen Conjugates During the First Eight Hours Following the Administration of Estrone-6,7-3H to Male Subjects. Probable Role of the Enterohepatic Circulation
The presence of an enterohepatic circulation for estrogens in the human is well established, but its possible function as an anatomic pool in which estrogens are distributed and from which they may be transferred has not been explored. To obtain evidence for a pool effect attributable to the enterohepatic circulation, a single dose of estrone-6,7-3H was administered to 4 normal male subjects, and urine was collected in hourly periods for 8 hr. Samples were analyzed for radioactive unconjugated estrone, and for radioactive sulfates and glucosiduronates of estrone, estradiol-17β and estriol. Radioactive estrone glucosiduronate was found to be quantitatively the most important conjugate excreted during the 8-hr period, exceeding the excretion of the other radioactive conjugates by a factor of 10. The excretion of each estrogen was plotted against time, and the curves so obtained were fitted using a mathematical model consisting either of 1 or the sum of 2 gamma density functions. Unconjugated estrone which does not enter the enterohepatic circulation was excreted in the form of 1 gamma density function, suggesting one pool of distribution. In contrast, the various estrogen sulfates and glucosiduronates which do enter the enterohepatic circulation were usually excreted in the form of the sum of 2 gamma density functions, suggesting an additional pool of distribution for these conjugates. Several considerations suggest that this additional pool is likely to be the enterohepatic circulation.