ABSTRACT

17β-hydroxysteroid dehydrogenases (17β -HSD) belong to two protein families: SDR (short chain dehydrogenase/reductase) and AKR (aldo-ketoreductase) and . Family members are known in all species (bacteria, plants, insects, vertebrates). By using NAD(P)⁺ or NAD(P)H as cofactors the enzymes catalyse oxidation and reduction reactions interconverting keto and hydroxy groups and thereby modulate the biological action of steroids. 17β -hydroxysteroid dehydrogenases are involved in carcinogenesis (e.g. breast and prostate cancer) as well as in the pathogenesis of Alzheimer’s disease, osteoporosis, pseudohermaphroditism and diabetes. Some 17β -HSD genes underwent duplication giving rise to non-functional pseudogenes. 17β -HSDs belonging to the SDR family are characterized by distinct sequence motifs (cofactor binding site: GxxxGxG, active center: Sx_nYxxxK, NNAG following the cofactor binding site, and PG close to the C-terminal end of the cofactor binding domain). Mutations of the enzymes allow understanding of reaction mechanisms and biochemical basis of diseases. The importance of 17β -HSDs can be explained from their broad substrate spectrum which includes beside others sugars, steroids, retinoids, and lipids. Their profound medical impact suggests the enzymes as new targets for drug development. This review on 17β-HSDs will concentrate on structure-function relationships, molecular basis of human diseases and genomic annotation.