Effects of ethynyl estradiol on liver microsomal mixed function oxygenase activity in male rats
Sweeney, G.D.; Cole, F.M.
Laboratory Investigation; A Journal of Technical Methods and Pathology 42(2): 231-235
1980
ISSN/ISBN: 0023-6837 PMID: 7354619 Document Number: 156879
Treatment of adult male rats with the hepatocarcinogen, ethynyl estradiol (EE), produces morphologic changes in the liver such as, are seen in more actively proliferating forms of this tissue. Because of the dependence of hepatic mixed function oxygenase (MFO) reactions on sex and stage of development, this aspect of liver function was studied under similar conditions of treatment. Adult male Fischer rats were fed ad lib powdered chow containing 0.5 or 5.0 mg of EE per kg of chow for periods from 4-20 wk. After 8 wk, cytochrome P-450 was decreased 30%, and the ethyl isocyanide binding spectrum was typical of the female. 7-Ethoxycoumarin-O-deethylase was reduced 5 times, but aryl hydrocarbon hydroxylase was reduced 20 times. This effect was present at 4 wk and maximal by 8 wk; it was more marked in animals receiving the higher dose of EE which corresponded to a daily burden of approximately 100 .mu.g/kg. When EE-treated animals received 2 inducing agents, phenobarbital (40 mg/kg, 2 times daily) and 3-methylcholanthrene (20 mg/kg, i.p. daily) for 3 days, aryl hydrocarbon hydroxylase was at least as inducible as in control animals. Other measures of MFO activity tended to show an after induction to before induction ratio similar to control animals but with absolute levels remaining lower in the estrogen-treated animals. Polyacrylamide gel electrophoresis of solubilized microsomal proteins showed decreased protein in the hemoprotein region from 48,000-58,000 daltons but showed a relative increase in protein in a distinct band at 49,000 daltons. Decreased MFO activity, with a disproportionate decrease in aryl hydrocarbon hydroxylase activity, was previously described in human fetal liver and in hyperplastic nodules from livers of rats treated with 2-acetylaminofluorene. Other studies on such tumor tissue have drawn attention to the high concentration of preneoplastic antigen, a protein which has subsequently been purified and shown to possess epoxide hydrase activity and a MW of 49,000 daltons. While EE treatment from 4-20 wk altered MFO activity to resemble that seen in more actively proliferating forms of liver tissue, the response of EE-treated animals to agents which induce MFO activity was more characteristic of adult liver.