Basic and translational research on proteinase-activated receptors: proteinase-activated receptors in female reproductive tissues and endometriosis.

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 PAR(1) (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 PAR(1) in the ovulatory process. In the endometrium, PAR(2) expression increases during the menstrual period. PAR(2) activation induces IL-8 production and cell proliferation in human endometrial stromal cells. PAR(1) 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 PAR(1) and PAR(2) 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.