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

Yutaka Osuga, Yasushi Hirota, Yuji Taketani
Journal of pharmacological sciences · 2008 · vol. 108(4) , pp. 422–425 · doi:10.1254/jphs.08r13fm · PMID:19098388 · W2025890114
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⚙ AI-generated summary by claude@2026-06, 2026-06-08 ⓘ

Thrombin-activated proteinase-activated receptors (PARs) 1 and 2 stimulate cytokine production and cell proliferation in ovarian and endometrial cells, suggesting roles in ovulation, menstruation, and endometriosis.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-09 · read from full text ⓘ

This minireview discusses the roles of proteinase-activated receptors (PAR1 and PAR2) in female reproductive tissues during the menstrual cycle, focusing on how thrombin- or PAR2-mediated activation affects inflammatory signaling and cellular behavior. It reports that thrombin-induced PAR1 activation in human granulosa cells increases IL-8 and MCP-1, while PAR2 expression rises in the endometrium and PAR2 activation in human endometrial stromal cells induces IL-8 production and cell proliferation, with PAR1 also stimulating proinflammatory cytokine production in stromal cells. The paper further states that PAR1 and PAR2 likely contribute to endometriosis because their activation induces inflammatory cytokine secretion and proliferation of stromal cells in endometriotic lesions, though it is a narrative review rather than a primary study. This paper is centrally about endometriosis — it argues that PAR1 and PAR2 activation promotes cytokine production and stromal proliferation in endometriotic lesions.

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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 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.
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Forum Minireview Basic and Translational Research on Proteinase-Activated Receptors: Proteinase-Activated Receptors in Female Reproductive Tissues and Endometriosis 2008 Volume 108 Issue 4 Pages 422-425 Details 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. © The Japanese Pharmacological Society 2008 Favorites & Alerts Recently viewed articles Predecessor

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Receptor, PAR-1 Receptor, PAR-2 Animals Cytokines Cytokines Endometriosis Endometrium Endometrium Endometrium Female Gene Expression Regulation Granulosa Cells Granulosa Cells Humans Ovulation Ovulation Receptor, PAR-1 Receptor, PAR-2

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