Induction of rat liver microsomal epoxide hydrolase by its endogenous substrate 16 alpha, 17 alpha-epoxyestra-1,3,5-trien-3-ol.
1. The influence of the endogenous steroid epoxides 16 alpha, 17 alpha-epoxyestra-1,3,5(10)-trien-3-ol (estroxide) and 16 alpha, 17 alpha-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.
Fändrich
F
F
Institute of Toxicology, University of Mainz, Germany.
Degiuli
B
B
Vogel-Bindel
U
U
Arand
M
M
Oesch
F
F
D015660:7-Alkoxycoumarin O-Dealkylase / Q000378:metabolism; D000818:Animals; D004790:Enzyme Induction / Q000187:drug effects; D004851:Epoxide Hydrolases / Q000096:biosynthesis* / Q000378:metabolism; D004852:Epoxy Compounds / Q000378:metabolism; D004964:Estriol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D005982:Glutathione Transferase / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D010088:Oxidoreductases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D004852:Epoxy Compounds; C021673:16 beta,17 beta-epoxy-1,3,5(10)-estratrien-3-ol; C013690:styrene oxide; D010088:Oxidoreductases; D015660:7-Alkoxycoumarin O-Dealkylase; C048338:trans-1,2-dihydrobenzene-1,2-diol dehydrogenase; D005982:Glutathione Transferase; D004851:Epoxide Hydrolases; D004964:Estriol