Drug-protein conjugates--V. Sex-linked differences in the metabolism and irreversible binding of 17 alpha-ethinylestradiol in the rat.
Sex-linked differences in the disposition, biotransformation, excretion and irreversible binding of [6, 7-3H]17 alpha-ethinylestradiol [( 3H]EE2) in Wistar rats have been observed. Three hours after i.v. administration of [3H]EE2 (5 micrograms/kg) the livers of males contained twice as much 3H-labelled material as those of females. The biliary metabolites were largely glucuronides in both sexes, but males also excreted arylsulphates. The principal metabolites liberated from biliary conjugates by enzymes were 2-hydroxyEE2 and 2-methoxyEE2 in females and males, respectively. Biliary elimination of 3H over 3 hr was slightly greater in males (P less than 0.05). Radiolabelled material was irreversibly bound to hepatic microsomal and soluble protein. The material bound to microsomes represented 0.24 +/- 0.07% (mean +/- S.D.) of the dose in males and 0.56 +/- 0.10% in females (P less than 0.001). Oxygenation of the steroid D-ring was not indicated, and 2-hydroxyEE2 appears to be the precursor of the reactive metabolite. The metabolic basis of the sex-linked difference in irreversible binding is discussed.
D000818:Animals; D001646:Bile / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D004997:Ethinyl Estradiol / Q000378:metabolism*; D005260:Female; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010053:Ovary / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012737:Sex Factors; D013737:Testis / Q000378:metabolism; D014018:Tissue Distribution
D004997:Ethinyl Estradiol