Dihydrotestosterone induces SREBP-1 expression and lipogenesis through the phosphoinositide 3-kinase/Akt pathway in HaCaT cells

Lipids Health Dis. 2012 Nov 15:11:156. doi: 10.1186/1476-511X-11-156.

Abstract

Background: The purpose of this study was to investigate the effects and mechanisms of dihydrotestosterone (DHT)-induced expression of sterol regulatory element binding protein-1 (SREBP-1), and the synthesis and secretion of lipids, in HaCaT cells. HaCaT cells were treated with DHT and either the phosphoinositide 3-kinase inhibitor LY294002 or the extracellular-signal-regulated kinase (ERK) inhibitor PD98059. Real time-PCR, Western blot, Oil Red staining and flow cytometry were employed to examine the mRNA and protein expressions of SREBP-1, the gene transcription of lipid synthesis, and lipid secretion in HaCaT cells.

Findings: We found that DHT upregulated mRNA and protein expressions of SREBP-1. DHT also significantly upregulated the transcription of lipid synthesis-related genes and increased lipid secretion, which can be inhibited by the addition of LY294002.

Conclusions: Collectively, these results indicate that DHT induces SREBP-1 expression and lipogenesis in HaCaT cells via activation of the phosphoinositide 3-kinase/Akt Pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Dihydrotestosterone / pharmacology*
  • Gene Expression / drug effects
  • Humans
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism
  • Lipogenesis / drug effects*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Signal Transduction / drug effects
  • Sterol Regulatory Element Binding Protein 1 / genetics*
  • Sterol Regulatory Element Binding Protein 1 / metabolism*

Substances

  • RNA, Messenger
  • SREBF1 protein, human
  • Sterol Regulatory Element Binding Protein 1
  • Dihydrotestosterone
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt