Regulation of steroid 5-α reductase type 2 (Srd5a2) by sterol regulatory element binding proteins and statin

Young Kyo Seo, Bing Zhu, Tae Il Jeon, Timothy F. Osborne

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

In this study, we show that sterol regulatory element binding proteins (SREBPs) regulate expression of Srd5a2, an enzyme that catalyzes the irreversible conversion of testosterone to dihydroxytestosterone in the male reproductive tract and is highly expressed in androgen-sensitive tissues such as the prostate and skin. We show that Srd5a2 is induced in livers and prostate from mice fed a chow diet supplemented with lovastatin plus ezitimibe (L/E), which increases the activity of nuclear SREBP-2. The three fold increase in Srd5a2 mRNA mediated by L/E treatment was accompanied by the induction of SREBP-2 binding to the Srd5a2 promoter detected by a ChIP-chip assay in liver. We identified a SREBP-2 responsive region within the first 300 upstream bases of the mouse Srd5a2 promoter by co-transfection assays which contain a site that bound SREBP-2 in vitro by an EMSA. Srd5a2 protein was also induced in cells over-expressing SREBP-2 in culture. The induction of Srd5a2 through SREBP-2 provides a mechanistic explanation for why even though statin therapy is effective in reducing cholesterol levels in treating hypercholesterolemia it does not compromise androgen production in clinical studies.

Original languageEnglish (US)
Pages (from-to)3133-3139
Number of pages7
JournalExperimental Cell Research
Volume315
Issue number18
DOIs
StatePublished - Nov 1 2009

    Fingerprint

Keywords

  • Androgen regulation
  • ChIP-chip assay
  • Srd5a2
  • SREBP-2
  • Statin
  • Transcription regulation

ASJC Scopus subject areas

  • Cell Biology

Cite this