Metabolism of Estrogens in the Gastrointestinal Tract of Swine. II. Orally Administered Estradiol-17β-D-Glucuronide3

Studies were conducted to determine the absorption and metabolic fate of orally administered 3H-estradiol-17 beta-glucuronide (3H-E2-G) in swine. Xylazine-tranquilized female pigs (5 to 6 wk old) were given .04, .4 or 4 mumol 3H-E2-G via stomach tube, and blood samples were collected from previously implanted jugular cannulas for 12 or 72 h. The entire gastrointestinal tract was removed from gilts euthanatized 12 h post-treatment, and free and conjugated estrogens were isolated from plasma and intestinal chyme by diethyl ether extraction and adsorption to Amberlite XAD-2 resin columns. After preparative thin layer chromatography of the conjugate fractions, the conjugates were cleaved by enzyme hydrolysis, solvolysis or acid hydrolysis. The freed estrogens were identified by thin layer chromatography. Plasma radioactivity peaked between 6 and 8 h after administration of the conjugate. None of the radioactivity in plasma was ether extractable. There was evidence for a decrease in absorption rate of radioactive estrogen in the high dosage group. The pattern of metabolites and urinary excretion or orally administered 3H-E2-G was similar to that reported for 14C-E2, except for the greater proportion of polar metabolites and delayed absorption, probably reflecting the need for the conjugate to be hydrolyzed first. The greater proportion of polar metabolites found in this study may have been due to the longer treatment period rather than the administration of the conjugated form of estradiol.