BILIARY AND URINARY METABOLITES OF 4-C¹⁴-PROGESTERONE IN HUMAN SUBJECTS*

Abstract

C14-progesterone was injected intravenously into 9 human subjects, 4 of whom had biliary fistulas. Following hydrolysis of steroid conjugates and continuous extraction with ether, the pooled urinary and pooled biliary extracts contained more than 50 per cent of the injected radioactivity. The extracts were separated into several fractions by counter-current distributions, followed by adsorption chromatography. Radioactive metabolites elutcd from alumina columns were characterized by isotope dilution with standard carriers in addition to chromatographic mobilities. Pregnanediol, allopregnanediol, pregnanolone and progesterone were identified in both urine and bile. Results indicate that hydroxylated metabolites of progesterone are eliminated mostly in the urine, while the corresponding ketonic compounds are excreted chiefly in the bile. THE principal pathway of the metabolism of progesterone is believed to be progesterone→pregnanedione→pregnanolone→pregnanediol,1 although small amounts of the corresponding allopregnane compounds are formed (1). It is important to note, however, that these conclusions are based on a recovery of only 15–30 per cent of administered progesterone as urinary metabolites. More recent experiments with C14-progesterone have indicated that one reason for the low recovery of metabolites in the urine is that substantial amounts enter the feces by way of the bile (2–5). For example, following the intravenous injection of 4-C14-progesterone into human subjects with bile fistulas, Sandberg and Slaunwhite (4) found that nearly 30 per cent of the radioactivity was excreted in the bile while 50 per cent was excreted in the urine. In normal subjects, 13 per cent of the injected radioactivity was excreted in the feces.