RRC ID 60005
Author Li Y, Zheng Q, Sun D, Cui X, Chen S, Bulbul A, Liu S, Yan Q.
Title Dehydroepiandrosterone stimulates inflammation and impairs ovarian functions of polycystic ovary syndrome.
Journal J. Cell. Physiol.
Abstract Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility in child-bearing-age women. It is characterized by ovulation dysfunction, polycystic ovaries, and hyperandrogenism. Inflammation is likely to be a crucial contributor to the pathogenesis of PCOS. However, the association between the inflammatory cytokines and the development of PCOS has not been reported. To explore the relationship between the inflammatory cytokines and PCOS, alterations of serum proteins in dehydroepiandrosterone (DHEA)-induced PCOS rats were screened by protein array, and the concentration of IFN-γ was further measured by using enzyme-linked immunosorbent assay (ELISA). DHEA-induced PCOS rats had a decreased level of IFN-γ compared with the control rats, which was restored partly in flutamide (an androgen receptor antagonist)-treated rats. Moreover, the level of IFN-γ in serum of patients with PCOS was also lower than that in healthy women. Using the ovarian granulosa cells (KGN), we demonstrated that DHEA downregulated the expression and secretion of IFN-γ in dose- and time-dependent manners, which could be restored to some extent by treating with flutamide. Furthermore, flutamide ameliorated the inhibitory effect on cell proliferation and promotive effect on cell apoptosis by DHEA. The results also revealed that IFN-γ promoted the proliferation but inhibited the apoptosis of KGN cells, which was suppressed by DHEA via activating the downstream PI3K/AKT signaling pathway. Taken together, these results showed that DHEA inhibited the proliferation and promoted the apoptosis of ovarian granulosa cells through downregulating the expression of IFN-γ which could be restored by flutamide, and IFN-γ may serve as a potential inflammatory biomarker for PCOS detection.
Volume 234(5)
Pages 7435-7447
Published 2019-5
DOI 10.1002/jcp.27501
PMID 30580448
MeSH Animals Apoptosis / drug effects Cell Line Dehydroepiandrosterone / physiology* Disease Models, Animal Down-Regulation / drug effects Female Granulosa Cells / drug effects Granulosa Cells / metabolism Humans Inflammation / chemically induced* Inflammation / metabolism Interferon-gamma / metabolism Ovary / drug effects* Ovary / metabolism* Polycystic Ovary Syndrome / metabolism* Polycystic Ovary Syndrome / pathology* Rats Rats, Sprague-Dawley Signal Transduction / drug effects
IF 4.522
Human and Animal Cells KGN(RCB1154)