Impaired CRH and urocortin expression and function in eutopic endometrium of women with endometriosis

Abstract

Context: Women with endometriosis have altered endometrial function. CRH and urocortin (Ucn) are neuropeptides produced by human endometrium and modulate endometrial decidualization. Objective: To evaluate endometrial mRNA expression of CRH and Ucn, their role in in vitro decidualization of cultured human endometrial stromal cells (HESCs) in patients with endometriosis, and the role of CRH receptors (CHR-Rs). Design: Obstetrics and Gynecology, University of Siena. Patients: Endometrial specimens were obtained from patients with and without endometriosis. Interventions: Endometrial biopsy obtained at both phases of menstrual cycle. In vitro decidualization of HESCs collected from endometriosis or control was done in the presence of CRH, Ucn, or CRH receptor type 1 (CRH-R1, antalarmin) or type 2 (CRH-R2, astressin 2b) antagonists. Outcome Measures: Endometrial mRNA expression of CRH and Ucn during endometrial cycle; prolactin, CRH-R1, and CRH-R2 mRNA expression during in vitro decidualization. Results: In healthy women CRH and Ucn expression were significantly higher (P < 0.05) in secretory than in proliferative phase; no differences were observed in endometriotic women. During in vitro decidualization, prolactinmRNAexpressionandrelease inendometriosiswaslowerthanincontrol(P< 0.001). CRHandUcnwereabletosignificantly increase (P<0.01) prolactin releaseonlyin controlgroup; moreover, in this group antalarmin reduced prolactin release (P < 0.01). CRH-R1 mRNA expression increased during in vitro decidualization of HESCs in control (P < 0.01) but not in endometriosis. Conclusions: Women with endometriosis show an impaired endometrial expression of CRH and Ucn mRNA,andtheseneuropeptidesarenomoreactive inmodulatingthein vitrodecidualizationofHESCs, associated with a reduced expression of CRH-R1 mRNA. Copyright © 2011 by The Endocrine Society.