Transcriptional regulation of human placental corticotropin-releasing factor by prostaglandins and estradiol

Khaled I. Dibbs, Eyal Anteby, Mary Ann Mallon, Yoel Sadovsky, Stuart Adler

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

The mechanism of labor initiation in humans has not been completely elucidated. Prostaglandins, estrogens, and corticotropin-releasing factor (CRF) have all been shown to affect uterine myocytes and enhance uterine contractility. There are also indications that these uterine regulators have additional effects on other sites involved in labor and that they may act in concert or, perhaps, by regulating each other. Therefore, we evaluated the CRF promoter for transcriptional regulation by prostaglandins and estrogens. Human placental choriocarcinoma cell lines were transfected with CRF- luciferase reporter genes and treated with prostaglandins. Prostaglandin E2 (PGE2), but not prostaglandin F(2α) (PGF(2α)), stimulated CRF-luciferase expression in choriocarcinoma cell lines via a cAMP-dependent pathway. A combination of transfections and in vitro binding studies tested for potential regulation of CRF by estrogen receptor (ER). ER neither regulated the CRF promoter nor interacted with steroid response half-sites from the CRF promoter. Our results provide a molecular regulatory link between PGE2 and CRF, two compounds that enhance uterine contractile function. Combined with the stimulation of prostaglandin release by CRF, these data support a potentially important 'feed-forward' regulatory loop involving CRF and PGE2 in parturition. In contrast, we found no evidence for direct effects of estrogens or PGF(2α) on CRF transcription.

Original languageEnglish
Pages (from-to)1285-1292
Number of pages8
JournalBiology of Reproduction
Volume57
Issue number6
DOIs
StatePublished - 1 Jan 1997
Externally publishedYes

ASJC Scopus subject areas

  • Reproductive Medicine

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