Follicle‐stimulating hormone promotes age‐related endometrial atrophy through cross‐talk with transforming growth factor beta signal transduction pathway

Aging Cell

Dan Zhang¹  Jingyi Li¹  Gufeng Xu¹  Runjv Zhang¹  Chengliang Zhou¹  Yeqing Qian¹  Yifeng Liu¹  Luting Chen¹  Bo Zhu¹  Xiaoqun Ye¹  Fan Qu¹  Xinmei Liu¹  Shuai Shi¹  Weijun Yang²  Jianzhong Sheng¹ 

[1] Key Laboratory of Reproductive Genetics, Zhejiang University, Ministry of Education, Hangzhou, China;Institute of Cell Biology and Genetics, College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China

关键词: aging;    atrophy;    autophagy;    follicle‐stimulating hormone;    menopause;    transforming growth factor beta;   

DOI  :  10.1111/acel.12278

来源: Wiley

【 摘 要 】

Summary

It is widely believed that endometrial atrophy in postmenopausal women is due to an age-related reduction in estrogen level. But the role of high circulating follicle-stimulating hormone (FSH) in postmenopausal syndrome is not clear. Here, we explored the role of high circulating FSH in physiological endometrial atrophy. We found that FSH exacerbated post-OVX endometrial atrophy in mice, and this effect was ameliorated by lowering FSH with Gonadotrophin-releasing hormone agonist (GnRHa). In vitro, FSH inhibited endometrial proliferation and promoted the apoptosis of primary cultured endometrial cells in a dose-dependent manner. In addition, upregulation of caspase3, caspase8, caspase9, autophagy-related proteins (ATG3, ATG5, ATG7, ATG12 and LC3) and downregulation of c-Jun were also observed in endometrial adenocytes. Furthermore, smad2 and smad3 showed a time-dependent activation in endometrial cells which can be partly inhibited by blocking the transforming growth factor beta receptor II (TβRII). In conclusion, FSH regulated endometrial atrophy by affecting the proliferation, autophagy and apoptosis of endometrial cells partly through activation of the transforming growth factor beta (TGFβ) pathway.

【 授权许可】

CC BY   
© 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

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