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Liver and Gastrointestinal Metabolism of Diethylstilbestrol in Sheep^{1, 2,}

University of Georgia, Athens 30601

Abstract

The metabolism of diethylstilbestrol (DES) monoethyl-1-¹⁴C by liver and gastrointestinal tissue was studied in five mature sheep. In vitro liver perfusions, everted intestinal sacs, and rumen mucosa incubation procedures were employed. Mean retention of radioactivity by the livers after a single passage of ¹⁴C-DES through the livers was 76.1%. Of the total radioactivity remaining in the perfusate after the initial passage, 38.5% was free DES and 61.5% was the glucuronide. Following a 1-hr. perfusion period 99.3% of the perfusate radioactivity was in the conjugate fraction and the perfusate contained approximately 50% more radioactivity indicating release of initially retained activity. Approximately 95.0% of the radioactivity present in the livers after the 1-hr. perfusion period was in the conjugate fraction. It was observed that rumen mucosa can form DES-glucuronide and that intestine can form and transport DES-glucuronide. Evidence for tissue hydrolysis of the glucuronide was not obtained.

¹ Published as Paper No. 881, University of Georgia Institute of Comparative Medicine, Department of Physiology and Pharmacology.

² This project supported in part by Lilly Research Laboratories grant.