The biotransformation of 17 alpha-ethynyl[3H]estradiol in the rat: irreversible binding and biliary metabolites.

1. The irreversible binding of metabolites of 17 alpha-ethynyl[6,7-3H]estradiol ([3H]EE2) to intracellular proteins, and the biliary metabolites of [3H]EE2, were studied in male rats. 2. Very low levels of irreversible binding to hepatic microsomal and soluble proteins were observed. 3. Approx. 75% of the radiolabelled material excreted in bile was present as beta-glucuronides and arylsulphate esters. 4. The compounds liberated from the biliary conjugates by enzymic hydrolysis consisted of EE2, 2-hydroxy-EE2, 16-hydroxy-EE2, 2-methoxy-EE2, 2-hydroxymestranol and at least three additional metabolites not fully identified. 2-Methoxy-EE2 was the principal metabolite. 5. EE2 and all its identified metabolites were excreted as both beta-glucuronides and arylsulphate esters. The glucuronide fraction contained a greater proportion of EE2, a lower proportion of 2-methoxy-EE2 and a lower ratio of 2-methoxy-EE2 to 2-hydroxymestranol than the arylsulphate fraction.