Expression, Localization, and Signaling of PGE2 and EP2/EP4 Receptors in Human Nonpregnant Endometrium across the Menstrual Cycle

Publisher Website
Google Scholar
Abstract
This study was designed to elucidate the sites of synthesis and action of PGE2 in the nonpregnant human uterus across the menstrual cycle. The sites of expression of PGE synthase and synthesis of PGE2 were investigated by immunohistochemis- try using full thickness uterine biopsies. Expression of PGE synthase and synthesis of PGE2 were localized to glandular epithelial and endothelial cells in both basalis and functio- nalis regions of the human endometrium. By contrast, stromal staining was predominantly localized in the functionalis layer. Some cyclical variation in expression of PGE synthase and PGE2 synthesis was observed, with reduced expression/ synthesis detected in the stromal compartment of the func- tionalis during the late secretory phase of the menstrual cycle. Subsequently, we assessed the site of action of PGE2 by in- vestigating the expression of two PGE2 receptor isoforms, namely EP2 and EP4. Cyclical variation in endometrial EP2 and EP4 receptor mRNA expression was quantified by Taq- Man quantitative RT-PCR using RNA isolated from endome- trial tissue collected across the menstrual cycle. No differ- ences in EP2 receptor mRNA expression were detected; however, EP4 receptor mRNA expression was significantly higher in late proliferative stage (P < 0.05) than in early, mid, and late secretory stage endometrium. Expression patterns of EP2 and EP4 receptors were localized by nonradioactive in situ hybridization using fluorescein isothiocyanate end- labeled oligonucleotide probes. Expression of both receptors was observed in endometrial glandular epithelial and vascu- lar cells, with no notable spatial or temporal variation. Fi- nally, signaling of EP2/EP4 receptors was assessed by inves- tigating cAMP generation in vitro after stimulation with PGE2. Endometrial cAMP generation in response to PGE2 was significantly greater in proliferative tissue compared with early and midsecretory stage tissue (3.77 0.85 vs. 1.96 0.28 and 1.38 0.23, respectively; P < 0.05). In conclusion, this study demonstrates glandular and vascular coexpression of PGE synthase, PGE2, EP2, and EP4 receptors and suggests an autocrine/paracrine role for PGE2 in epithelial/endothelial cell function in the human endometrium. (J Clin Endocrinol Metab 86: 4453- 4459, 2001)

This publication has 0 references indexed in Scilit: