6,7-3H-Estriol-16α-glucosiduronate-14C was administered to eight women (nine studies) by several routes: both injection and infusion (300 min) into the cubital vein, injection into the portal vein system, ingestion and instillation into the duodenum, jejunum, and ileum. Urine, collected from 0-2, 2-4, 4-8, 8-12, and 12-24 hr, was analyzed by countercurrent distribution for its content of radioactive 3- and 16-glucosiduronate (E3-3Gl,E3-16Gl) and sulfoglucosiduronate (E3-3S,16Gl) of estriol as well as for 3H/14C ratio of each conjugate. After peripheral injection 50-60% of the injected E3-16Gl was excreted unchanged along with about 5% as E3-3S,16Gl with an unchanged 3H/14C ratio, indicating direct sulfation of the injected E3-16Gl. During a 300 min infusion, urinary excretion closely resembled that following injection. But 2-4 hr after the end of the infusion excretion of E3-3S, 16Gl stopped, excretion of E3-3Gl (17%/24 hr) with an elevated 3H/14C ratio started, and excretion of E3-16Gl continued (70%/24 hr), but with a rapidly increasing 3H/14C ratio. This indicated sequestration in a sluggishly metabolizing compartment where two processes occurred: (a) extensive hydrolysis of E3-16Gl followed by reconjugation at either C3 or C16 with unlabeled uridine diphosphate glucuronic acid (UDPGA), thereby increasing the 3H/14C ratio; and (b) transconjugation from C16 to C3, thereby producing E3-3Gl with finite 3H/14C ratios. Instillation into various segments of the small intestine produced results qualitatively similar to those after intravenous infusion, whereas ingestion and intraportal injection resembled peripheral intravenous injection. Therefore, we have postulated the possibility of an enteric circulation (in addition to an enterohepatic circulation) in which the steroid or its conjugates are transported into the small intestine in the succus entericus, modified, and then reabsorbed and excreted in the urine-a process which requires several hours.
N. Inoue, A. A. Sandberg, J. B. Graham, W. R. Slaunwhite Jr.
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