Prostaglandin E2Stimulates Aromatase Expression in Endometriosis-Derived Stromal Cells1

L. S. Noble, Noble LS, Luis S. Noble, K Takayama, Takayama K, Kazuto Takayama, Khaled M. Zeitoun, K M Zeitoun, Zeitoun KM, J. Michael Putman, J M Putman, Putman JM, D A Johns, Johns DA, D. Alan Johns, Margaret M. Hinshelwood, Hinshelwood MM, M M Hinshelwood, Agarwal VR, Veena R. Agarwal, V R Agarwal, Y Zhao, Zhao Y, Ying Zhao, Carr BR, Bruce R. Carr, B R Carr, Bulun Se, Serdar E. Bulun, S E Bulun
The Journal of clinical endocrinology and metabolism · 1997 · vol. 82(2) , pp. 600–606 · doi:10.1210/jcem.82.2.3783 · PMID:9024261 · W2109563515
article OA: closed CC0 ⤵ 282 in-corpus citations
View on OpenAlex View on PubMed View at publisher
⚙ AI-generated summary by gemini-2.5-flash-lite, 2026-06-08 ⓘ

Prostaglandin E2 significantly stimulates aromatase activity and messenger RNA expression in endometriosis-derived stromal cells primarily via promoter II, suggesting a key role in local estrogen biosynthesis.

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

Abstract

C19 steroids are converted to estrogens by aromatase P450 (P450arom). Aromatase expression in humans is regulated by use of tissue-specific promoters in the placenta (promoter I.1), adipose tissue (promoters I.4, I.3, and II), and gonads (promoter II). The use of each promoter gives rise to a population of P450arom messenger ribonucleic acid (mRNA) species with a unique untranslated 5'-terminus. Aromatase is not expressed in the endometrium of disease-free women. We demonstrated, however, the presence of P450arom mRNA in pelvic endometriotic implants and eutopic endometrial curettings of women with endometriosis. In the current report, aromatase activity and P450arom gene expression were investigated in cultured stromal cells derived from eutopic endometrium and ovarian endometriomas of women with pelvic endometriosis. We also investigated the hormonal regulation of aromatase expression and alternative promoter use in these cells. The effects of interleukin-1 beta (IL-1 beta), IL-2, IL-6, IL-11, oncostatin M, IL-15, tumor necrosis factor-alpha, PGE2, estradiol, R5020, dexamethasone, and dibutyryl cAMP (Bt2cAMP) on aromatase activity in endometriosis-derived stromal cells were assessed. We chose treatments with PGs and ILs because of the inflammatory nature of endometriosis. PGE2 stimulated aromatase activity in endometriosis-derived stromal cells by 19- to 44-fold (37-221 pmol/mg protein-4 h), whereas Bt2cAMP induction was 26- to 60-fold the baseline level. No stimulation was observed by estradiol or R5020 or by IL-1 beta, IL-2, IL-6, IL-11, IL-15, or TNF alpha in the presence or absence of glucocorticoids. A modest induction of aromatase activity (2-fold) was observed in dexamethasone- plus oncostatin M-treated cells. These changes in aromatase activity were accompanied by comparable changes in the levels of P450arom mRNA levels, determined by a quantitative reverse transcription-PCR method. Promoter-specific 5'-ends of P450arom transcripts in total RNA from endometriosis-derived stromal cells treated with PGE2 and Bt2cAMP were amplified employing a novel modified rapid amplification of cDNA5'-ends/Southern hybridization method using exon-specific oligonucleotide probes. The majority of P450arom transcripts in these cells contained the gonadal-type promoter II-specific sequences, whereas very few transcripts contained adipose-type promoter I.3- and I.4-specific sequences. PGE2 appears to be the most potent known stimulator of aromatase in endometriosis. Aromatase expression in PGE2-stimulated stromal cells of endometriosis is regulated primarily by the classically located promoter II, which, in turn, is regulated by cAMP. As PGE2 is known to increase intracellular cAMP levels, estrogen biosynthesis in endometriosis may be primarily regulated by PGE2 that is locally produced. Consequent local estrogen production may promote the growth of endometriotic implants.

My notes (saved in your browser only)

Condition tags

endometriosis

MeSH descriptors

Aromatase Dinoprostone Endometriosis Endometrium Ovarian Diseases Aromatase Aromatase Cells, Cultured Dinoprostone Endometriosis Endometriosis Endometrium Endometrium Female Humans Ovarian Diseases Ovarian Diseases Promoter Regions, Genetic RNA, Messenger RNA, Messenger

Citation neighborhood (2-hop)

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. Outer rings show 2-hop neighbours — papers reached through the immediate citers/citees. [ collapse to 1-hop ]

References (41)

Cited by (50)

Source provenance

europepmc
last seen: 2026-10-07T06:10:45.703000+00:00
openalex
last seen: 2026-06-10T17:14:06.276822+00:00
pubmed
last seen: 2026-05-13T22:10:52.568893+00:00
License: CC0 · commercial use OK