RRC ID 65734
Author Zheng Q, Li Y, Zhang D, Cui X, Dai K, Yang Y, Liu S, Tan J, Yan Q.
Title ANP promotes proliferation and inhibits apoptosis of ovarian granulosa cells by NPRA/PGRMC1/EGFR complex and improves ovary functions of PCOS rats.
Journal Cell Death Dis
Abstract Polycystic ovary syndrome (PCOS) is a complicated reproductive endocrine disease characterized by polycystic ovaries, hyperandrogenism and anovulation. It is one of the main causes of infertility. RU486 is an antagonist of progesterone receptor, and most commonly used as a contraceptive. However, whether RU486 is correlated with PCOS remains unclear. Atrial natriuretic peptide (ANP) is a small peptide with natriuretic and diuretic functions, and its availability to be used in PCOS treatment is unknown. Here, we showed that the serum ANP level was lower in PCOS patients than that in healthy women, and it was also decreased in the serum and ovarian tissues of RU486-induced PCOS rats compared with the control rats. We also found that RU486 inhibited the proliferation and promoted the apoptosis of human KGN ovarian granulosa cells by downregulating progesterone receptor membrane component 1 (PGRMC1). Meantime, ANP promoted the proliferation and inhibited the apoptosis of KGN cells through upregulating ANP receptor A (NPRA). The promotive effects of ANP on ovarian functions were mediated through the formation of an NPRA/PGRMC1/EGFR complex, which further activated MAPK/ERK signaling and transcription factor AP1. Moreover, ANP treatment reversed the PCOS symptoms, and improved the fertility of RU486-induced PCOS rats. Collectively, these findings highlight that RU486 is associated with the pathogenesis of PCOS, and ANP treatment may be a promising therapeutic option for PCOS.
Volume 8(10)
Pages e3145
Published 2017-10-26
DOI 10.1038/cddis.2017.494
PII cddis2017494
PMID 29072679
PMC PMC5682660
MeSH Animals Apoptosis / drug effects Apoptosis / physiology Atrial Natriuretic Factor / blood* Cell Proliferation / drug effects Cell Proliferation / physiology ErbB Receptors / metabolism* Female Granulosa Cells / metabolism* Granulosa Cells / pathology Humans Membrane Proteins / metabolism* Mifepristone / pharmacology Ovary / metabolism Ovary / pathology Ovary / physiopathology Polycystic Ovary Syndrome / blood Polycystic Ovary Syndrome / genetics Polycystic Ovary Syndrome / pathology Polycystic Ovary Syndrome / physiopathology* Rats Rats, Sprague-Dawley Receptors, Progesterone / metabolism* Transfection
IF 6.304
Human and Animal Cells KGN(RCB1154)