The biotransformation of 17α-ethynyl[³H]estradiol in the rat: Irreversible binding and biliary metabolites

Abstract

1. The irreversible binding of metabolites of 17α-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 β-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 β-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.