Androgen metabolism in sheep.

ABSTRACT

3H-Testosterone (3H-T) plus 14C-androst-4-ene-3,17-dione (A-dione) and 3H-epi-testosterone (17alpha-hydroxy-4-androsten-3-one) (epiT) plus 14C-T were injected intravenously into two male sheep with bile fistulae, respectively. Urine and bile samples were collected at intervals for 4-8 hours and analyzed by the use of DEAE-Sephadex A-25 and Lipidex 5000 columns, TLC, and paper chromatography; the aglycones were identified by co-crystallization with authentic standards. Five fractions were obtained from urine and bile unconjugated, glucosiduronates, sulfates, sulfo-glucosiduronates and disulfates. In urine, the major conjugates were glucosiduronates, while sulfates predominated in bile. About 80-90% of recovered radioactivity was found to be either glucosiduronates or sulfates. Among the metabolites identified, epi-T was the principal one, accounting for 10-15% of the administered doses. Conversion to 17alpha-hydroxysteroids thus appears to be a major route of metabolism of the androgens administered in sheep. Other metabolites in the glucosiduronate and sulfate fractions were androsterone, etiocholanolone (3alpha-hydroxy-5beta-androstan-17-one), 5beta-androstane-3alpha,17beta-diol, two unknown diols and polar metabolites. The results indicated that androgen metabolism is somewhat unusual in sheep, as compared with other animals and the human.