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Metabolism of 17β-Estradiol in ACI Rat Liver and Mammary Gland After Chronic Estradiol Treatment

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Hormonal Carcinogenesis IV

Summary

A comparative study of the effects of chronic 17β-estradiol (E2) treatment on microsomal oxidation and conjugation of E2 via Phase I and II enzymes in the ACI rat mammary gland (MG) and liver was performed. NADPH-dependent oxidation of E2 was not detected in the MG, but was readily measured in the liver. Oxidation was not altered by chronic E2 treatment. Ascorbic acid stimulated E2 oxidation (non-enzymatically) in MG microsomes, but had no effect in the liver. Hepatic but not MG NADP(H):quinone oxidoreductase and glutathione S-transferase activities increased 4.0- and 2.0-fold, respectively, after 6 weeks (w) of treatment. MG catalase activity was decreased 64% after 28 w of E2 treatment, when the rats had developed 100% incidence of MG adenocarcinomas. Moreover, the activities of phenolsulfotransferase SULT1A1 and fatty acyl-CoA:E2-acyltransferase ACO:E2 decreased by 95 and 80%, respectively, in the MG but not in liver. Decreases in these enzymes were maximal after 6 w and preceded induction of MG tumors. Collectively, these data indicate that E2 regulates the expression of antioxidant and E2-metabolizing enzymes differentially in the ACI rat liver and MG. The decreased activities of SULT1A1 and ACO:E2 may favor accumulation of E2 available for receptor binding and conversion to catechol estrogens, both of which are implicated in E2-induced mammary oncogenesis.

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Authors and Affiliations

  1. Laboratory for Cellular and Biochemical Toxicology, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA

    Sonia Mesia-Vela

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  1. Sonia Mesia-Vela
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  2. Rosa I Sanchez
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  3. Kenneth R. Reuhl
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  4. Allan H. Conney
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  5. Frederick C. Kauffman
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Editors and Affiliations

  1. Division of Etiology and Prevention of Hormonal Cancers, The University of Kansas Medical Center, 3901 Rainbow Boulevard, 2010 Breidenthal, Kansas City, KS, 66160-7417

    Jonathan J. Li (Profesor of Pharmacology, Toxicology and Therapeutics and Director) & Sara A. Li (Associate Research Professor of Pharmacology, Toxicology and Therapeutics) (Profesor of Pharmacology, Toxicology and Therapeutics and Director) &  (Associate Research Professor of Pharmacology, Toxicology and Therapeutics)

  2. Departmento de Patologia, Facultad de Medicina y Odontologia, Camino de Vera s/n, Valencia, 46071, Spain

    Antonio Llombart-Bosch (Director) (Director)

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Mesia-Vela, S., Sanchez, R.I., Reuhl, K.R., Conney, A.H., Kauffman, F.C. (2005). Metabolism of 17β-Estradiol in ACI Rat Liver and Mammary Gland After Chronic Estradiol Treatment. In: Li, J.J., Li, S.A., Llombart-Bosch, A. (eds) Hormonal Carcinogenesis IV. Springer, Boston, MA. https://doi.org/10.1007/0-387-23761-5_35

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  • DOI: https://doi.org/10.1007/0-387-23761-5_35

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-0-387-23783-1

  • Online ISBN: 978-0-387-23761-9

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