The abnormal expression of kisspeptin regulates pro-inflammatory cytokines, cell viability and apoptosis of macrophages in hyperandrogenism induced by testosterone

Background Increasing evidences have proposed that kisspeptins may be involved in polycystic ovary syndrome (PCOS) including hyperandrogenism. This work aimed to investigate the effect of kisspeptin in hyperandrogenism induced by testosterone. Methods The most suitable concentration of testosterone to induce hyperandrogenism was determined by detecting the mRNA changes of kisspeptin and macrophages pro-inflammatory cytokines. The role of kisspeptin in hyperandrogenism was investigated by RT-PCR of kisspeptin and pro-inflammatory cytokines, by CCK-8 of cell viability, by Annexin V-FITC/PI staining followed by flow cytometry of apoptosis, by ELISA of pro-inflammatory cytokines and by Western blot of kisspeptin and antiapoptotic Bcl-2 and proapoptotic Bax. Results We found that testosterone elevated kisspeptin, pro-inflammatory cytokines expressions and nitrite release in excessive androgen stimulated macrophages and further inhibited the macrophages cell viability and increased apoptosis. Kisspeptin knockdown reversed the tendency caused by testosterone and decreased apoptosis in macrophages treated with testosterone. Moreover, mRNA and protein expression levels of Bcl-2 and Bax were assessed. We showed a reduction in Bcl-2 mRNA and protein expression levels and an overexpression of Bax mRNA and protein expression levels.Kiss1silencing reversed Bcl-2 and Bax expressions. Conclusion Kisspeptin inactivation confers resistance in hyperandrogenism by inhibiting pro-inflammatory cytokines expressions and apoptosis. Our results may help to comprehend the role of kisspeptin in the mechanisms of hyperandrogenism.

Automated summary

The study demonstrates that kisspeptin plays a role in regulating the expression of pro-inflammatory cytokines and apoptosis induced by hyperandrogenism, suggesting that kisspeptin inactivation confers resistance to hyperandrogenism by inhibiting pro-inflammatory cytokines expressions and apoptosis.