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  • Title: Similarities and differences in the glucuronidation of estradiol and estrone by UDP-glucuronosyltransferase in liver microsomes from male and female rats.
    Author: Zhu BT, Suchar LA, Huang MT, Conney AH.
    Journal: Biochem Pharmacol; 1996 May 03; 51(9):1195-202. PubMed ID: 8645343.
    Abstract:
    In this study, we evaluated the effects of pH, in vitro inhibitors, in vivo enzyme inducers, age, and sex on the glucuronidation of estradiol and estrone by rat liver microsomes. Although the pH dependence curves for the glucuronidation of estradiol and estrone were similar, the pH dependence curves for these estrogens by liver microsomes from adult male rats were very different from those by liver microsomes from adult female rats. These results suggest that liver microsomes from adult male and have different estrogen glucuronosyltransferases. Liver microsomes from immature or adult female rats catalyzed the glucuronidation of estrone and estradiol more rapidly than liver microsomes from age-matched male rats. Intraperitoneal injection of sodium phenobarbital (75 mg/kg/day) or dexamethasone (75 mg/kg/day) into immature or adult male or female rats for 3-4 days resulted in a 33-58% increase in liver microsomal glucuronosyltransferase activity for estradiol, but there was little or no stimulatory effect on glucuronosyltransferase activity for estrone. Treatment of immature or adult male or female rats with 3-methylcholanthrene (25 mg/kg/day) for 3-4 days did not stimulate liver microsomal glucuronosyltransferase activity for estradiol or estrone, but the glucuronidation of 4-nitrophenol was stimulated several-fold. The in vitro addition of testosterone had a strong inhibitory effect on the glucuronidation of estradiol and estrone by liver microsomes from both adult male and female rats, whereas the in vitro addition of 4-nitrophenol had a slightly greater inhibitory effect on the glucuronidation of estradiol and estrone by adult male liver microsomes than by adult female liver microsomes. In conclusion, our results suggest that male and female rat livers have different estrogen glucuronosyltransferases and that the glucuronidation of estradiol, estrone, and 4-nitrophenol is catalyzed by different glucuronosyltransferases that are under different regulatory control.
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