title: Endometrial corticotropin-releasing hormone. Its potential autocrine and paracrine actions.
abstract: Corticotropin-releasing hormone (CRH) is expressed at several peripheral tissues including normal epithelial cells of human and rodent uterus. However, its biological role is unknown in both species. To clarify this role we studied the regulation of CRH promoter in endometrial cells. We performed homologous transfection experiments in Ishikawa cells, a human endometrial cell line, using a 0.9-kb fragment of the 5'-flanking region of human CRH gene coupled to luciferase. We found that the activity of the 5'-flanking region of the CRH gene is stimulated by cAMP and EGF and inhibited in a receptor-mediated, dose-dependent fashion by estradiol and dexamethasone. The antiglucocorticoid RU 486 acted as a glucocorticoid agonist suppressing CRH gene activation, whereas progesterone was devoid of any activity. Prostaglandin E2 and interleukins-1 and -6 stimulated CRH activation, and the prostanoid inhibitor indomethacin suppressed it, most probably by inhibiting endogenous prostaglandins. These findings suggest that endometrial CRH gene expression may be under the negative control of estrogens and glucocorticoids and under the positive control of PGE2, IL-1, and IL-6. Considering the involvement of CRH in proinflammatory phenomena, we postulate that endometrial CRH, in association with uterine prostanoids and cytokines, may participate in intrauterine inflammatory processes of early pregnancy, such as decidualization and blastocyst implantation.
authors.affiliation: Department of Pharmacology, Medical School, University of Crete, Stavrakia, Iraklion, Greece.
authors.forename: E
authors.initials: E
authors.lastname: Zoumakis
authors.forename: A
authors.initials: A
authors.lastname: Makrigiannakis
authors.forename: A N
authors.initials: AN
authors.lastname: Margioris
authors.forename: C
authors.initials: C
authors.lastname: Stournaras
authors.forename: A
authors.initials: A
authors.lastname: Gravanis
mesh_terms: D000818:Animals; D019898:Autocrine Communication / Q000502:physiology*; D003346:Corticotropin-Releasing Hormone / Q000502:physiology*; D004717:Endometrium / Q000378:metabolism*; D005260:Female; D006801:Humans; D019899:Paracrine Communication / Q000502:physiology*; D011247:Pregnancy
chemical_list: D003346:Corticotropin-Releasing Hormone