The role of an enterohepatic system in the metabolism of 17beta-estradiol-17-glucosiduronate in the human female.

Abstract

17β-Estradiol-6,73H-17-glucosiduronate (E217G) was injected iv in a single dose into 3 normal women and 3 women with biliary drainage via T-tube. Urine and, where applicable, bile was collected over various periods of time and the conjugated metabolites were analyzed by Amberlite resin, DEAE-Sephadex, Celite and thinlayer chromatography, together with selective enzymatic hydrolysis, derivative formation and crystallization with unlabeled carriers. In the normal women 62–70% of the dose appeared in the urine in 24 hr with >80% in 72 hr. Some 95% of the urinary 3H within 2–3 hr after injection (17–48% dose) was E217G and the remainder was 17β-estradiol-3-sulfate-17-glucosiduronate (E23S17G). Over about 2–6 hr a lag in 3 excretion occurred, the latter 2 conjugates virtually disappeared and estrone-3-glucosiduronate (E13G) plus estradiol-3-glucosiduronate (E23G) appeared in the urine. Beyond 6 hr E13G and E23G increased cumulatively and were by far the main metabolites up to 72 hr. No E217G was excreted at these later times but very small amounts of other glucosiduronates, e.g. those of estriol (E3) and 16-epiestriol (16-epiE3), were present. In the T-tube patients E217G was the major labeled conjugate in the urine within 3 hr, accompanied by small amounts of E23S17G. Major amounts of E23S17G appeared in the bile unaccompanied by E217G. An unidentified conjugate, probably a sulfoglucosiduronate, also appeared in variable amounts in the bile. Beyond 3–6 hr the T-tube patients excreted variable amounts of E13G and E23G in the urine, these probably arising from biliary E23S17G which had bypassed the collection tube, and/or from precursors transported into the intestine via the succus entericus. Administration of 3-E23Sl7G directly into the duodenum of a normal female was followed by negligible urinary excretion of 3H up to 6 hr. After that time the urinary metabolite pattern was similar to that seen after 6 hr following iv 3H-E217G into normal women. Thus the metabolism of E217G to urinary E13G and E23G appears to occur in the intestine from biliary E23Sl7G via deconjugation and partial conversion of E2 to Er before or after reconjugation with endogenous glucuronyl groups at C-3. About 7% of the dose was excreted in the bile when labeled E13G was injected iv into a woman with biliary drainage via T-tube.