Temporal expression and signalling of prostacyclin receptor in the human endometrium across the menstrual cycle

Abstract

Prostacyclin (PGI2) synthesis and function in the human uterus has been implicated in the regulation of the process of normal and dysfunctional menstruation. PGI2 synthesis is elevated during normal menstruation and is also associated with blood loss in women who suffer from heavy menses. This study was designed to outline further the role of PGI2 in menstruation by investigating the temporal pattern and site of expression of prostaglandin I synthase (PGIS) and the prostacyclin receptor (IP receptor) in the non-pregnant human endometrium across the menstrual cycle. Quantitative RT-PCR demonstrated increased expression of PGIS and IP receptor during the menstrual phase of the cycle compared with all other phases (P < 0.05). Furthermore, PGIS and IP receptor were localised to the glandular epithelium, stromal and endothelial cells in the basal and functional layers of the endometrium. Functionality of the IP receptor in the human endometrium was assessed by measuring cAMP generation following treatment with 100 nmol l-1 of the PGI2 analogue, iloprost. cAMP generation was significantly higher in endometrial tissue collected during the proliferative compared with the secretory phase of the menstrual cycle (P < 0.05). In conclusion, this study has confirmed increased expression and signalling of PGIS and IP receptor during the menstrual phase and outlines a potential autocrine/paracrine role for PGI2 on several cellular compartments in the endometrium including the endothelium. This may underscore a pivotal role for PGI2 receptor signalling in normal and dysfunctional menstruation.