Transactivation of Steroidogenic Acute Regulatory Protein in Human Endometriotic Stromal Cells Is Mediated by the Prostaglandin EP2 Receptor

H Sunny Sun, Kuei-Yang Hsiao, Kuei‐Yang Hsiao, Chih-Chao Hsu, Meng-Hsing Wu, Meng‐Hsing Wu, Shaw-Jenq Tsai, Shaw‐Jenq Tsai
Endocrinology · 2003 · vol. 144(9) , pp. 3934–3942 · doi:10.1210/en.2003-0289 · PMID:12933667 · W2137867018
article OA: bronze CC0 ⤵ 68 in-corpus citations
📄 Open PDF View on OpenAlex View on PubMed View at publisher
⚙ AI-generated summary by claude@2026-06, 2026-06-08 ⓘ

Prostaglandin E2 stimulates steroidogenic acute regulatory protein expression in human endometriotic stromal cells via EP2 receptor, PKA, and CREB-mediated histone acetylation of the StAR promoter.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

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) E(2) stimulates StAR protein expression at the cellular and molecular levels. PGE(2) 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 PGE(2), and this was mirrored by an increase in nascent StAR RNA transcription. Treatment with the histone deacetylase inhibitor, tricostatin A, enhanced PGE(2)-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 PGE(2)-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.

My notes (saved in your browser only)

Condition tags

endometriosis

MeSH descriptors

Endometrium Phosphoproteins Receptors, Prostaglandin E Stromal Cells Acetylation Activating Transcription Factor 2 Base Sequence Cells, Cultured Chromatin Chromatin Cyclic AMP-Dependent Protein Kinases Cyclic AMP-Dependent Protein Kinases Cyclic AMP Response Element-Binding Protein Cyclic AMP Response Element-Binding Protein Endometrium Endometrium Female Gene Expression Gene Expression Histones

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (51)

Cited by (50)

Source provenance

europepmc
last seen: 2026-06-04T01:30:01.192114+00:00
openalex
last seen: 2026-06-04T00:00:01.174412+00:00
pubmed
last seen: 2026-05-13T22:12:44.121522+00:00
License: CC0 · commercial use OK