The key role of 17 beta-hydroxysteroid dehydrogenases in sex steroid biology.
17 beta-Hydroxysteroid dehydrogenase (17 beta-HSD) controls the last step in the formation of all androgens and all estrogens. This crucial role of 17 beta-HSD is performed by at least five 17 beta-HSD isoenzymes having individual cell-specific expression, substrate specificity, regulation mechanisms, and reductive or oxidative catalytic activity. Both estrogenic and androgenic 17 beta-HSD activities were found in all 25 rhesus monkey and 15 human peripheral intracrine tissues examined. Type 1 17 beta-HSD is a protein of 327 amino acids catalyzing the formation of 17 beta-estradiol from estrone. Its x-ray structure was the first to be determined among mammalian steroidogenic enzymes. Initially crystallized with NAD, the crystal structure of type 1 17 beta-HSD has just been determined as a complex with 17 beta-estradiol, thereby illustrating the conformation of the substrate-binding site. Type 2 17 beta-HSD degrades 17 beta-estradiol into estrone and testosterone into androstenedione, and type 4 17 beta-HSD mainly degrades 17 beta-estradiol into estrone and androst-5-ene-3 beta, 17 beta-diol into dehydroepiandrosterone. Types 3 and 5 17 beta-HSD, on the other hand, catalyze the formation of testosterone from androstenedione in the testis and peripheral tissues, respectively. The various types of human 17 beta-HSD, because of their tissue-specific expression and substrate specificity, provide each peripheral cell with the necessary mechanisms to control the level of intracellular androgens and/or estrogens, a new area of hormonal control that we call intracrinology.
Labrie
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MRC Group in Molecular Endocrinology, CHUL Research Center, Ste-Foy, Québec, Canada.
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Lin
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Labrie
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Simard
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Breton
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Bélanger
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D015067:17-Hydroxysteroid Dehydrogenases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000728:Androgens / Q000378:metabolism; D000818:Animals; D018360:Crystallography, X-Ray; D003687:Dehydroepiandrosterone / Q000378:metabolism; D004746:Enoyl-CoA Hydratase; D004958:Estradiol / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism; D005260:Female; D012739:Gonadal Steroid Hormones / Q000378:metabolism*; D000882:Haplorhini; D006801:Humans; D006836:Hydro-Lyases; D007527:Isoenzymes; D008297:Male; D008958:Models, Molecular; D009097:Multienzyme Complexes; D005810:Multigene Family; D064029:Peroxisomal Multifunctional Protein-2; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D011487:Protein Conformation; D013256:Steroids / Q000378:metabolism*; D013739:Testosterone / Q000378:metabolism; D014018:Tissue Distribution; D014162:Transfection
D000728:Androgens; D004967:Estrogens; D012739:Gonadal Steroid Hormones; D007527:Isoenzymes; D009097:Multienzyme Complexes; D013256:Steroids; D013739:Testosterone; D003687:Dehydroepiandrosterone; D004958:Estradiol; D015067:17-Hydroxysteroid Dehydrogenases; D006836:Hydro-Lyases; D064029:Peroxisomal Multifunctional Protein-2; C104587:HSD17B4 protein, human; D004746:Enoyl-CoA Hydratase