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Estrogen Metabolism as a Regulator of Estrogen Action in the Mammary Gland

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Abstract

Estrogen action in the target cells is dependent on estrogen receptor activity and intracellular estrogen concentration, which, in turn, is affected by the serum concentration and local metabolism in these cells. During the reproductive years the main source of estrogens is the ovarian follicles, but in postmenopausal women most of the estrogens are formed in peripheral tissues. 17β-hydroxysteroid dehydrogenases (17HSDs)6 catalyze the reaction between 17β-hydroxysteroids and 17-ketosteroids, and several distinct 17HSD isoenzymes have been characterized. 17HSD type 1 catalyzes the reaction from low-activity estrone to high-activity estradiol. The type 2 enzyme has an opposite activity, thereby reducing the exposure of tissues to estrogen action. 17HSD type 1 is expressed both in steroidogenic tissues and in the target tissues of steroid action, such as normal and malignant breast tissue, where it may be responsible for maintaining the high intracellular estradiol concentration seen in breast cancer specimens. Therefore, 17HSD type 1 inhibitors may be useful in the treatment and/or prevention of estrogen-dependent malignancies, such as breast cancer. This article deals mainly with 17HSD types 1 and 2 and their role in estrogen action in breast tissue.

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Authors and Affiliations

  1. Biocenter Oulu and WHO Collaborating Centre for Research on Reproductive Health, University of Oulu, Oulu, Finland

    Minna Miettinen, Veli Isomaa, Hellevi Peltoketo & Pirkko Vihko

  2. Biocenter Oulu and Department of Biochemistry, University of Oulu, Oulu, Finland

    Hellevi Peltoketo

  3. Hauptman-Woodward Medical Research Institute Inc., Buffalo, New York

    Debashis Ghosh

  4. Roswell Park Cancer Institute, Buffalo, New York

    Debashis Ghosh

  5. Department of Biosciences, Division of Biochemistry, University of Helsinki, Helsinki, Finland

    Pirkko Vihko

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Miettinen, M., Isomaa, V., Peltoketo, H. et al. Estrogen Metabolism as a Regulator of Estrogen Action in the Mammary Gland. J Mammary Gland Biol Neoplasia 5, 259–270 (2000). https://doi.org/10.1023/A:1009542710520

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