NDLI: KLF15 Is a transcriptional regulator of the human 17beta-hydroxysteroid dehydrogenase type 5 gene. A potential link between regulation of testosterone production and fat stores in women.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Du, Xiaofei Rosenfield, Robert L. Qin, Kenan
Description	Country affiliation: United States Author Affiliation: Du X ( Section of Pediatric Endocrinology, 5839 South Maryland Avenue, MC 5053, Chicago, Illinois 60637, USA.)
Abstract	CONTEXT: Kruppel-like factor 15 (KLF15) is a newly discovered transcription factor that plays an important role in glucose homeostasis and lipid accumulation in cells. We present evidence for KLF15 as a transcriptional regulator of the human 17beta-hydroxysteroid dehydrogenase type 5 gene (HSD17B5) and its potential role in the pathogenesis of hyperandrogenism. OBJECTIVE: The aim was to investigate the molecular mechanism of HSD17B5 regulation. METHODS: Diverse molecular biology techniques were used. DESIGN AND RESULTS: We identified a KLF15 binding site in the HSD17B5 promoter by using luciferase promoter constructs, EMSA, and chromatin immunoprecipitation assays. Overexpression of KLF15 increased HSD17B5 promoter activity and testosterone formation at least 3-fold in cultured H295R cells. Insulin increased KLF15 mRNA expression according to real-time RT-PCR and increased HSD17B5 promoter activity according to luciferase assays. KLF15 overexpression in combination with insulin, glucocorticoid, and cAMP stimulated adipogenesis in H295R cells. In silico and RT-PCR analyses showed that the KLF15 gene promoter undergoes alternative splicing in a tissue-specific manner. Comparison of the HSD17B5 promoter in seven different species revealed that the KLF15 binding site has no human homolog in species other than orangutans. CONCLUSIONS: KLF15 is potentially a novel link between the regulation of testosterone production and fat stores by insulin in humans.
ISSN	0021972X
e-ISSN	19457197
DOI	10.1210/jc.2009-0139
Journal	The Journal of Clinical Endocrinology & Metabolism
Issue Number	7
Volume Number	94
Language	English
Publisher	Oxford University Press
Publisher Date	2009-07-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	17-hydroxysteroid Dehydrogenases Genetics Adipose Tissue Metabolism Gene Expression Regulation, Enzymologic Kruppel-like Transcription Factors Physiology Nuclear Proteins Testosterone 3-hydroxysteroid Dehydrogenases Animals Cells, Cultured Drug Effects Hydroxyprostaglandin Dehydrogenases Insulin Pharmacology Lipid Metabolism Molecular Sequence Data Promoter Regions, Genetic Sequence Homology, Nucleic Acid Sex Factors Transcription Factors Transcriptional Activation Research Support, N.i.h., Extramural Discipline Endocrinology Discipline Metabolism
Content Type	Text
Resource Type	Article
Subject	Biochemistry (medical) Endocrinology, Diabetes and Metabolism Clinical Biochemistry Biochemistry Endocrinology

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