Effect of TNF-alpha on endometrial glucose transporter-4 expression in patients with polycystic ovary syndrome through nuclear factor-kappa B signaling pathway activation.

Abstract

The present study aimed to investigate the possible mechanism of action of tumor necrosis factor-alpha (TNF-α) in endometrial glucose transporter-4 (GLUT-4) expression regulation by detecting the expression levels of endometrial inflammatory factors and GLUT-4 in patients with polycystic ovary syndrome (PCOS). A total of 140 patients were included in this study and divided into four groups: the PCOS group, the obesity + PCOS group, the normal group, and the obesity group (n = 35 each). The general clinical data of all patients were collected, and their expression levels of TNF-α, nuclear factor kappa B p65 (NF-κBp65), and GLUT-4 in the endometrium were tested via immunohistochemistry. Endometrial stromal cells were cultured in vitro and treated with TNF-α or pyrrolidine dithiocarbamate (PDTC) + TNF-α, and the expression levels of NF-κBp65, phospho-NF-κBp65 (p-NF-κBp65), and GLUT-4 were tested using Western blotting (WB) before and after treatment. As a result, we got: 1) Compared with the normal group, the abundance of the protein for TNF-α and NF-κBp65 in the endometrium of the patients with PCOS was elevated, while the expression level of GLUT-4 was decreased; the difference was statistically different (P < 0.05). The comparison between the obesity + PCOS group and the PCOS group yielded the same results. 2) According to the WB results, compared with the normal group, the abundance of the protein for endometrial GLUT-4 was decreased in the PCOS group, and the expression levels of p-NF-κBp65 and NF-κBp65 were increased in the obesity + PCOS group; the differences were statistically different (P < 0.05). The addition of TNF-α could decrease the abundance of the protein for GLUT-4 and increase the abundance of the protein for p-NF-κBp65. After treatment with PDTC + TNF-α, the abundance of the protein for p-NF-κBp65 decreased and GLUT-4 increased compared with the TNF-α group; these values were close to those of the control group. We concluded that the abundance of the proteins for local inflammatory factors in the endometrial cells of patients with PCOS was increased, indicating that TNF-α could affect the expression of endometrial GLUT-4 in such patients by activating the p-NF-κBp65 signaling pathway.