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J Clin Endocrinol Metab. 2009 Jul;94(7):2594-601. doi: 10.1210/jc.2009-0139. Epub 2009 Apr 14.

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.

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  • 1Section 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.

PMID:
19366843
[PubMed - indexed for MEDLINE]
PMCID:
PMC2708951
Free PMC Article

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