Effect of Dietary 2(3)-tert-Butyl-4-hydroxyanisole on the Metabolism and Action of Estradiol and Estrone in Female CD-1 Mice

摘要: Abstract Administration of 0.75% 2(3)- tert -butyl-4-hydroxyanisole (BHA) in AIN-76A diet to female CD-1 mice for 3 weeks increased liver microsomal glucuronidation estradiol, estrone, 4-aminophenol, and 4-nitrophenol by 103, 187, 162, 92%, respectively (at pH 7.4). The overall rate NADPH-dependent metabolism estradiol estrone microsomes BHA-treated animals as determined substrate disappearance was 20–40% over that from control animals. 2-hydroxylation (the major metabolic pathway) 24–38%, the formation 6α-hydroxyestradiol plus 6β-hydroxyestradiol 90–115%, 6β-hydroxyestrone (a minor metabolite formed mice) approximately 370% controls. In contrast, BHA administration had little or no effect on 4- 16α-hydroxylated metabolites. Measurable levels were observed serum uterus ovariectomized at 30 min after a single i.p. injection 100 300 ng these decreased 30–60% fed 18 days prior estrogen. Feeding BHA-supplemented inhibited uterotropic (45 75 ng/mouse, once daily days) compared response diet. also estradiol- estrone-stimulated [ H]thymidine incorporation into uterine DNA. conclusion, feeding 2–3 activities enzymes catalyze uridine 5′-diphosphoglucuronic acid-dependent oxidation enhanced vivo estrogens, their action.