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17ß-Hydroxysteroid dehydrogenases (17ß-HSDs) as therapeutic targets: protein structures, functions, and recent progress in inhibitor development.
Marchais-Oberwinkler, Sandrine; Henn, Claudia; Möller, Gabriele; Klein, Tobias; Negri, Matthias; Oster, Alexander; Spadaro, Alessandro; Werth, Ruth; Wetzel, Marie; Xu, Kuiying; Frotscher, Martin; Hartmann, Rolf W; Adamski, Jerzy.
Afiliação
  • Marchais-Oberwinkler S; Saarland University, Pharmaceutical and Medicinal Chemistry, PO Box 15 11 50, 66041 Saarbrücken, Germany.
J Steroid Biochem Mol Biol ; 125(1-2): 66-82, 2011 May.
Article em En | MEDLINE | ID: mdl-21193039
17ß-Hydroxysteroid dehydrogenases (17ß-HSDs) are oxidoreductases, which play a key role in estrogen and androgen steroid metabolism by catalyzing final steps of the steroid biosynthesis. Up to now, 14 different subtypes have been identified in mammals, which catalyze NAD(P)H or NAD(P)(+) dependent reductions/oxidations at the 17-position of the steroid. Depending on their reductive or oxidative activities, they modulate the intracellular concentration of inactive and active steroids. As the genomic mechanism of steroid action involves binding to a steroid nuclear receptor, 17ß-HSDs act like pre-receptor molecular switches. 17ß-HSDs are thus key enzymes implicated in the different functions of the reproductive tissues in both males and females. The crucial role of estrogens and androgens in the genesis and development of hormone dependent diseases is well recognized. Considering the pivotal role of 17ß-HSDs in steroid hormone modulation and their substrate specificity, these proteins are promising therapeutic targets for diseases like breast cancer, endometriosis, osteoporosis, and prostate cancer. The selective inhibition of the concerned enzymes might provide an effective treatment and a good alternative to the existing endocrine therapies. Herein, we give an overview of functional and structural aspects for the different 17ß-HSDs. We focus on steroidal and non-steroidal inhibitors recently published for each subtype and report on existing animal models for the different 17ß-HSDs and the respective diseases. Article from the Special issue on Targeted Inhibitors.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Inibidores Enzimáticos / 17-Hidroxiesteroide Desidrogenases / Isoenzimas Limite: Animals / Female / Humans / Male Idioma: En Revista: J Steroid Biochem Mol Biol Ano de publicação: 2011 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Inibidores Enzimáticos / 17-Hidroxiesteroide Desidrogenases / Isoenzimas Limite: Animals / Female / Humans / Male Idioma: En Revista: J Steroid Biochem Mol Biol Ano de publicação: 2011 Tipo de documento: Article