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Title: Progesterone Receptor Serves the Ovary as a Trigger of Ovulation and a Terminator of Inflammation.

Authors: Park, Chan Jin; Lin, Po-Ching; Zhou, Sherry; Barakat, Radwa; Bashir, Shah Tauseef; Choi, Jeong Moon; Cacioppo, Joseph A; Oakley, Oliver R; Duffy, Diane M; Lydon, John P; Ko, CheMyong J

Published In Cell Rep, (2020 04 14)

Abstract: Ovulation is triggered by the gonadotropin surge that induces the expression of two key genes, progesterone receptor (Pgr) and prostaglandin-endoperoxide synthase 2 (Ptgs2), in the granulosa cells of preovulatory follicles. Their gene products PGR and PTGS2 activate two separate pathways that are both essential for successful ovulation. Here, we show that the PGR plays an additional essential role: it attenuates ovulatory inflammation by diminishing the gonadotropin surge-induced Ptgs2 expression. PGR indirectly terminates Ptgs2 expression and PGE2 synthesis in granulosa cells by inhibiting the nuclear factor κB (NF-κB), a transcription factor required for Ptgs2 expression. When the expression of PGR is ablated in granulosa cells, the ovary undergoes a hyperinflammatory condition manifested by excessive PGE2 synthesis, immune cell infiltration, oxidative damage, and neoplastic transformation of ovarian cells. The PGR-driven termination of PTGS2 expression may protect the ovary from ovulatory inflammation.

PubMed ID: 32294429 Exiting the NIEHS site

MeSH Terms: Animals; Cyclooxygenase 2/genetics; Cyclooxygenase 2/metabolism; Female; Gene Expression Regulation/genetics; Gene Expression/genetics; Granulosa Cells/metabolism; Inflammation/metabolism; Mice; Mice, Inbred C57BL; NF-kappa B/metabolism; Ovarian Follicle/metabolism; Ovary/metabolism*; Ovulation/metabolism*; Progesterone/genetics; Progesterone/metabolism; RNA, Messenger/genetics; Receptors, Progesterone/genetics; Receptors, Progesterone/metabolism; Receptors, Progesterone/physiology*; Transcription Factors/metabolism

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