Basic and Translational Research on Proteinase-Activated Receptors: Proteinase-Activated Receptors in Female Reproductive Tissues and Endometriosis

Abstract

During the menstrual cycle, dynamic morphological changes are observed in the ovarian follicle and the endometrium. These changes are associated with the onset of the inflammatory response in which many proteinases play various roles. Thrombin-induced activation of PAR1 (proteinase-activated receptor 1) stimulates the production of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) in human granulosa cells, suggesting a possible role for PAR1 in the ovulatory process. In the endometrium, PAR2 expression increases during the menstrual period. PAR2 activation induces IL-8 production and cell proliferation in human endometrial stromal cells. PAR1 also stimulates proinflammatory cytokine production in human endometrial stromal cells. Thus, the PARs may be important in directing the dynamic changes of the endometrium. PARs also appear to play a role in endometriosis, a common gynecological disease, since activation of PAR1 and PAR2 induces the secretion of inflammatory cytokines and the proliferation of stromal cells in endometriotic lesions. Taken together, PARs appear to play diverse roles in the human reproductive organs.