Metformin inhibits estradiol and progesterone-induced decidualization of endometrial stromal cells by regulating expression of progesterone receptor, cytokines and matrix metalloproteinases - 09/12/18
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Abstract |
Background |
Polycystic ovary syndrome (PCOS) is a serious threat for reproductive-aged women. Metformin has been used for the treatment of PCOS. However, its molecular mechanism in decidualization process of PCOS has not been well featured.
Methods |
RT-qPCR analysis was used to detect expression patterns of progesterone receptor (PGR), estradiol receptor alpha (ERα), Cytokeratin 8 and Vimentin in endometrial tissues of PCOS and non-PCOS patients. RT-qPCR assay was also employed to determine mRNA expression of prolactin, Insulin-like growth factor-binding protein 1 (IGFBP-1), matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP9). Cytokine secretion were measured by matching ELISA kits. Protein expression of p-ERK1/2, ERK1/2, p-p38 MAPK, p38 MAPK, and PGR (PGRA and PGRB) was tested by western blot assay.
Results |
PGR expression was upregulated in PCOS patients. Metformin alleviated estradiol (E2) and progesterone (P4) (EP)-induced decidualization of endometrial stromal cells. Abnormal cytokine secretion was observed in EP-stimulated endometrial stromal cells in the absence or presence of metfromin. Metformin suppressed EP-induced MMP-2 and MMP-9 upregulation. Metformin alleviated EP-triggered p38 MAPK inactivation and PGR (PGRA and PGRB) expression. Metfromin had no effect on ERK1/2 signaling in EP-stimulated endometrial stromal cells.
Conclusion |
Metformin alleviated EP-induced decidualization of endometrial stromal cells by modulating secretion of multiple cytokines, inhibiting expression of MMP-2 and MMP-9, activating p38-MAPK signaling and reducing PGR expression, providing a deep insight into the molecular basis of metfromin therapy for PCOS patients.
Le texte complet de cet article est disponible en PDF.Keywords : Polycystic ovary syndrome, Metfromin, Decidualization, Progesterone receptor, Cytokines, p38-MAPK, ERK1/2
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Vol 109
P. 1578-1585 - janvier 2019 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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