Role of 17 beta-hydroxysteroid dehydrogenase type 1 in endocrine and intracrine estradiol biosynthesis.
Enzymes with 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) activity catalyse reactions between the low-active female sex steroid, estrone, and the more potent estradiol, for example. 17 beta-HSD activity is essential for glandular (endocrine) sex hormone biosynthesis, but it is also present in several extra-gonadal tissues. Hence, 17 beta-HSD enzymes also take part in local (intracrine) estradiol production in the target tissues of estrogen action. Four distinct 17 beta-HSD isozymes have been characterized so far, and the data strongly suggests that different 17 beta-HSD isozymes have distinct roles in endocrine and intracrine metabolism of sex steroids. Current data suggest that 17 beta-HSD type 1 is the principal isoenzyme involved in glandular estradiol production both in humans and rodents. During ovarian follicular development and luteinization, rat 17 beta-HSD type 1 is regulated by gonadotropins, and the effects of gonadotropins are modulated by steroid hormones and paracrine growth factors. Human 17 beta-HSD type 1 favors the reduction reaction, thereby converting estrone to estradiol both in vitro and in cultured cells. Hence, the enzymatic properties of the enzyme are also in line with its suggested role in estradiol biosynthesis. Interestingly, 17 beta-HSD type 1 is also expressed in certain target tissues of estrogen action such as normal and malignant human breast and endometrium. Hence, 17 beta-HSD type 1 could be one of the factors leading to a relatively high tissue/plasma ratio of estradiol in breast cancer tissues of postmenopausal women. We conclude that 17 beta-HSD type 1 has a central role in regulating the circulating estradiol concentration as well as its local production in estrogen target cells.
Biocenter Oulu, University of Oulu, Finland.
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Poutanen
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Isomaa
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Peltoketo
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Vihko
D015067:17-Hydroxysteroid Dehydrogenases / Q000502:physiology*; D000818:Animals; D001940:Breast / Q000201:enzymology; D004958:Estradiol / Q000096:biosynthesis*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D005796:Genes; D006801:Humans; D007527:Isoenzymes / Q000502:physiology; D010053:Ovary / Q000201:enzymology; D010920:Placenta / Q000201:enzymology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats
D007527:Isoenzymes; D012333:RNA, Messenger; D004958:Estradiol; D015067:17-Hydroxysteroid Dehydrogenases