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Expression of hepatic and ovarian cytochrome P450 during estrous cycle in rats

  • Toxicogenomics
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Abstract

It is known that gender differences in drug metabolism are largely attributed to changes in sex and growth hormones. Serum concentrations of estradiol, progesterone, prolactin, follicle-stimulating hormone, and luteinizing hormone change markedly during the human menstrual cycle and the rat estrous cycle. However, little information is available regarding the effects of the human menstrual cycle or the rat estrous cycle on expression and activity of cytochrome P450 (CYP) isoforms. The present study was carried out to determine the expression and activity of CYP-dependent drug-metabolizing enzymes in the liver and ovary during the estrous cycle. The expression and activity of microsomal CYP isoforms (CYP1A1, CYP1A2, CYP1B1, CYP2B1, CYP2C11, CYP2C12, CYP2E1, CYP3A1, CYP3A2, and CYP4A), cytochrome b5 and NADPH-dependent CYP reductase in the liver and ovary were measured in female rats in diestrus and proestrus. Our results indicated that hepatic and ovarian expression and activity of CYP isoforms, cytochrome b5, and NADPH-dependent CYP reductase were not different between diestrus and proestrus, although serum estradiol concentration and uterus weight were markedly increased in the proestrus phase. These results suggest that the cytochrome P450-dependent system is not sensitive to changes in the estrous cycle, and further studies are warranted to determine the effects of the estrous cycle on in vivo metabolism of xenobiotics.

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Acknowledgments

This work was supported by the Priority Research Centers Program (2009-0093815) through the Research Foundation of Korea (NRF) grant, funded by the Korean Government (MEST) and by a grant from the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (A101836).

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Correspondence to Kiho Lee or Sang Kyum Kim.

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S. Y. Lee and S. J. Oh contributed equally to this work.

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Lee, S.Y., Oh, S.J., Yun, K.U. et al. Expression of hepatic and ovarian cytochrome P450 during estrous cycle in rats. Arch Toxicol 86, 75–85 (2012). https://doi.org/10.1007/s00204-011-0730-1

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  • DOI: https://doi.org/10.1007/s00204-011-0730-1

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