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Metabolism of Estrogens in the Gastrointestinal Tract of Swine. II. Orally Administered Estradiol-17ß-D-Glucuronide^1,2,3,

Purdue University⁶, West Lafayette, IN 47907

Abstract

Studies were conducted to determine the absorption and metabolic fate of orally administered ³H-estradiol-17ß-glucuronide (³H-E₂-G) in swine. Xylazine-tranquilized female pigs (5 to 6 wk old) were given .04, .4 or 4 µimol 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.

¹ Journal Paper No. 7409, Agr. Exp. Sta., Purdue Univ., West Lafayette, IN. 2 Research supported in part by DHEW/Public

² Research supported in part by DHEW/Public Health Service, FDA, Contract 74-136.

³ The authors appreciate the assistance provided by Project Officers Dr. George Graber and Dr. Dave Batson. Thanks are also expressed to Martha Johnson and Ms Anne Hollister for technical assistance.

⁴ Present address: FDA, Rockville MD.

⁵ Present address: Southern Research Institute, 2000 Ninth Ave. South, Birmingham, AL 35205.

⁶ Abbreviations used in this paper are: ³ H-estradiol-17ß-D-glucuronide, ³H-E₂-G; estradiol-17ß-D-glucuronide, E₂-G; estradiol-17, E₂ ; estrone, E₁ jestriol, E₃ ; estrone-3-sulfate, E₁-S; estradiol-3-sulfate, E₂-S; estriol-3-suIfate, E₂-S; estrone-3-glucuronide, E₁-G.