Induction of rat liver microsomal epoxide hydrolase by its endogenous substrate 16α, 17α-epoxyestra-1,3,5-trien-3-ol

Abstract

1. The influence of the endogenous steroid epoxides 16α, 17α-epoxyestra-1,3,5(10)-trien-3-ol (estroxide) and 16α, 17α-expoxiandrost-4-en-3-one (androstene oxide) and their metabolic precursors estra-1,3,5(10), 16-tetraen-3-ol (estratetraenol) and androsta-4. 16-dien-3-one (androstadienone) on the specific activities of hepatic microsomal and soluble epoxide hydrolase, glutathione S-transferase, dihydrodiol dehydrogenase, and 7-ethoxycoumarin deethylase was investigated in the male Sprague-Dawley rat.

2. Both estroxide and estratetraenol induced microsomal epoxide hydrolase activity towards styrene oxide and estroxide itself 2-2·5-fold and glutathione conjugation of 1-chloro-2,4-dinitrobenzene (CDNB) 1·6-fold after intraperitoneal administration of a high dose of compound (300 mg per kg of body weight).

3. In addition, estroxide decreased 7-ethoxycoumarin deethylation down to 20% of the activity observed in the untreated rat, whereas estratetraenol enhanced the activity of soluble epoxide hydrolase towards trans-stilbene oxide by a factor of 1·7.

4. In contrast, neither androstene oxide nor androstadienone showed a significant influence on any of the parameters under investigation. Dihydrodiol dehydrogenase was not significantly changed by any of the treatments.