ETA-mediated anti-TNF-? therapy ameliorates the phenotype of PCOS model induced by letrozole.

ABSTRACT: Chronic inflammation is a typical characteristic of polycystic ovary syndrome (PCOS), in which, tumor necrosis factor (TNF)-? plays an important role. We investigated whether anti-TNF-? therapy can alleviate the core phenotypes of PCOS. In pubertal female Wistar rats, release pellets of letrozole (LET) were administered continuously for 90 days to induce PCOS-like phenotypes, followed by treatment with etanercept (ETA), a TNF-? inhibitor. ETA significantly inhibited increases in body weight and androgen, TNF-?, and MCP-1 levels, excessive recruitment of lipid droplets, altered levels of pre-adipose differentiation markers, and abnormal development of follicles. In addition, TNF-? and testosterone (T) levels in the rat sera were significantly positively correlated. Further experiments were performed to investigate the relationship between TNF-? and androgen. Persistent exposure of the RAW 264.7 cell line to low doses of testosterone significantly enhanced TNF-? expression and activated the NF-?B signaling pathway, which were blocked by ETA. Furthermore, treatment with TNF-? promoted the production of testosterone in KGN granulosa cells by reducing CYP19A1 expression, whereas ETA treatment blocked this process. In conclusion, anti-TNF-? therapy with ETA may be an efficient method to alleviate PCOS, whose underlying mechanism may be associated with its ability to reduce excessive androgen levels.

SUBMITTER: Lang Q 

PROVIDER: S-EPMC6553850 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature