Estrogen metabolism as a regulator of estrogen action in the mammary gland

Estrogen action in the target cells is dependent on estrogen receptor activ ity and intracellular estrogen concentration, which, in turn, is affected b y the serum concentration and local metabolism in these cells. During the r eproductive years the main source of estrogens is the ovarian follicles, bu t in postmenopausal women most of the estrogens are formed in peripheral ti ssues. 17 beta -hydroxysteroid dehydrogenases (17HSDs)(6) catalyze the reac tion between 17 beta -hydroxysteroids and 17-ketosteroids, and several dist inct 17HSD isoenzymes have been characterized. 17HSD type 1 catalyzes the r eaction from low-activity estrone to high-activity estradiol. The type 2 en zyme has an opposite activity, thereby reducing the exposure of tissues to estrogen action. 17HSD type 1 is expressed both in steroidogenic tissues an d in the target tissues of steroid action, such as normal and malignant bre ast tissue, where it may be responsible for maintaining the high intracellu lar estradiol concentration seen in breast cancer specimens. Therefore, 17H SD type 1 inhibitors may be useful in the treatment and/ or prevention of e strogen-dependent malignancies, such as breast cancer. This article deals m ainly with 17HSD types 1 and 2 and their role in estrogen action in breast tissue.