The metabolic fate of estrone in bile fistula dogs.

It has been repeatedly demonstrated that, following the administration of estrogen to human or animal subjects, the hormone disappears rapidly from the organism and only a small quantity of the original compound or its metabolites can be recovered in crystalline form from the urine (2). On the other hand, Cantarow et al. (3) detected in the bile of dogs with external bile fistula as much as 90 to 95 per cent of the biological activity of the estrone or a-estradiol which had been injected intravenously. Since bioassay had been performed directly on the bile without resort to fractionation procedures, it was thought desirable to pursue the problem of biliary excretion of estrogens along chemical lines. Accordingly, a total quantity of 1.476 gm. of estrone acetate (containing 1.278 gm. as estrone equivalent to 18,000,OOO mouse units of estrogenic activity) was dissolved in oil and injected intramuscularly into three external bile fistula dogs. The bile, urine, and feces were collected and extracted; 79 mg. of estrone and 18 mg. of cr-estradiol were isolated in crystalline form from the bile; considerably less estrogenic material as determined by bioassay was contained in the urine or feces. A detailed report is given below. Table I lists the estrogenic activity of the phenolic material derived from the bile, urine, and feces respectively; bioassay of unfractionated bile was also performed. Inspection shows that (a) considerably more estrogen was excreted in the bile than in the urine; a small but significant amount of estrogen appeared in the feces; (b) most of the estrogenic material of the bile and of the feces was present in a free or uncombined form; much of the estrogenic material in the urine was present in conjugated form, but the ratio of free to conjugated estrogen varied considerably. Table II indicates the distribution of the estrogenic activity of the various extracts between the ketonic and non-ketonic weakly acidic phenols and the strongly acidic phenols. Hydrolysates of the conjugated phenolic material of the bile and feces were not partitioned because of the