Transactivation of steroidogenic acute regulatory protein in human endometriotic stromal cells is mediated by the prostaglandin EP2 receptor

H. Sunny Sun, Kuei Yang Hsiao, Chih Chao Hsu, Meng Hsing Wu, Shaw Jenq Tsai

Research output: Contribution to journalArticlepeer-review

86 Citations (Scopus)

Abstract

Steroidogenic acute regulatory protein (StAR) regulates the first committed step in the biosynthesis of steroids, and thus aberrant expression of StAR in endometriotic implants plays a critical role in the etiology of endometriosis. However, the mechanism responsible for abnormal expression of StAR in ectopic endometriotic tissues remains unknown. In the present study, we demonstrate that prostaglandin (PG) E2 stimulates StAR protein expression at the cellular and molecular levels. PGE2 caused a rapid increase in StAR expression that involves activation of the EP2 receptor-coupled protein kinase A pathway. Activation of EP2 receptor-induced phosphorylation of ERK and cAMP response element binding protein (CREB). However, activation of ERK did not involve in CREB phosphorylation or concomitantly StAR expression. Phosphorylation of CREB induced by PGE 2 increased the recruitment of CREB binding protein and thus histone H3 acetylation. Chromatin immunoprecipitation experiments showed that acetylated histone H3 bound to the proximal region of the StAR promoter was increased after 30 min treatment with PGE2, and this was mirrored by an increase in nascent StAR RNA transcription. Treatment with the histone deacetylase inhibitor, tricostatin A, enhanced PGE2-induced nascent StAR RNA transcription. We conclude that increased histone H3 acetylation involving the EP2 receptor, protein kinase A, CREB, and CREB binding protein is responsible for PGE2-induced StAR gene activation in endometriotic stromal cells. Our current report may provide new insights in understanding mechanism of abnormally local production of estrogen and the etiology of endometriosis.

Original languageEnglish
Pages (from-to)3934-3942
Number of pages9
JournalEndocrinology
Volume144
Issue number9
DOIs
Publication statusPublished - 2003 Sep 1

All Science Journal Classification (ASJC) codes

  • Endocrinology

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