Endocrine, Metabolic & Immune Disorders-Drug Targets

(Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders)

Emilio Jirillo  
Universitá degli Studi di Bari
Dipartimento di Clinica Medica
Immunologia e Malattie Infettive
Sezione di Microbiologia e Immunologia
Piazza Giulio Cesare-Policlinico


Roles of Type 10 17beta-Hydroxysteroid Dehydrogenase in Intracrinology and Metabolism of Isoleucine and Fatty Acids

Author(s): X.- Y. He and S.- Y. Yang

Affiliation: NYS Institute for BasicResearch in Developmental Disabilities, 1050 Forest Hill Road, StatenIsland, New York 10314, USA.


Human type 10 17β -hydroxysteroid dehydrogenase (HSD) is a homotetrameric protein located in mitochondria. This enzyme was alternatively named short chain L-3-hydroxyacyl-CoA dehydrogenase (SCHSD). This NAD(H)- dependent dehydrogenase is essential for the metabolism of branched-chain fatty acids and isoleucine, and is expressed in a variety of tissues, e.g., prostate, brain, liver, and heart. This enzyme inactivates 17β -estradiol and exhibits a strong oxidative 3α-HSD activity to convert 5α-androstanediol and allopregnanolone into 5α-dihydrotestosterone (5α-DHT) and 5α-dihydroprogesterone, respectively, in living cells. Certain malignant prostatic epithelial cells and activated astrocytes in Alzheimers disease patients brain contain extraordinarily high levels of this enzyme. This mitochondrial dehydrogenase enables prostate cancer cells to generate 5α-DHT in the absence of testosterone. Its inactivation of allopregnanolone is important to the modulation of GABA(A) receptor. Among steroidogenic enzymes 17β-HSD10 plays a significant part in the intracrinology. Although this protein has an affinity for amyloid-βpeptide, its role in the pathogenesis of Alzheimers disease is far from clear. Additional knowledge of this versatile enzyme would provide the foundation for designing new drugs aimed at treating some neurological diseases and certain types of cancers.

Keywords: Metabolism of sex steroids and Neurosteroids, prostate cancer, short-chain L-3-hydroxyacyl-CoA dehydrogenase, branched-chain fatty acid oxidation, mental retardation, Alzheimer's disease

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Article Details

Page: [95 - 102]
Pages: 8
DOI: 10.2174/187153006776056639