The role of androgen in autophagy of granulosa cells from PCOS

Abstract

Hyperandrogenism is one of the most common causes for anovulation in women and increases the risk for metabolic disorder in PCOS patients. Autophagy plays an important role in dysfunction of endocrine and anovulation. However, the relationship between hyperandrogenism and autophagy in human granulosa cells of PCOS patients remains unclear. By collecting granulosa cells from PCOS patients and non-PCOS patients, we found that the abundance of autophagy-related genes ATG5, ATG7, BECN1 mRNA and the ratio of autophagy marker protein light chain 3B II/I (LC3 II/I) were significantly increased whereas the abundance of the autophagy substrate SQSTM1/p62 was decreased in ovarian granulosa cells from PCOS patients. Furthermore, we demonstrated that BECN1 mRNA abundance in human granulosa cells positively correlated with the basal level of serum total testosterone and androgen up-regulated the abundance of BECN1 mRNA and the ratio of LC3II/LC3I in a dose-dependent manner in cultured granulosa cells. These observations indicated that androgen-induced activation of autophagy may play an important role in the development of PCOS and to explore the autophagy mechanisms involved in PCOS yield new insight into the pathophysiology and therapy of the disorder.

摘要

高雄激素血症是女性无排卵最常见的原因之一, 并增加多囊卵巢综合征患者代谢紊乱的风险。自噬在内分泌功能障碍和无排卵中起重要作用。然而, PCOS患者颗粒细胞自噬与高雄激素血症的关系尚不清楚。通过收集PCOS患者与非PCOS患者, 我们发现在PCOS患者中许多与自噬相关的基因ATG5、ATG7、BECN1 mRNA和自噬标记蛋白轻链3B II/I (LC3 II/I) 显著增加, 而许多自噬基质 SQSTM1/p62 减少。此外, 我们还发现人颗粒细胞中BECN1 mRNA的浓度与血清总睾酮和雄激素的基础水平呈正相关, 在体外培养的颗粒细胞中, BECN1 mRNA的浓度和LC3II/LC3I呈剂量依赖。这些观察结果表明, 雄激素诱导的自噬激活可能在多囊卵巢综合征发生发展中发挥重要作用, 探讨多囊卵巢综合征的自噬机制为多囊卵巢综合征病理生理学和治疗提供新思路。

The Chinese abstracts are translated by Prof. Dr. Xiangyan Ruan and her team: Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China.

Keywords:

• Polycystic ovary syndrome
• hyperandrogenism
• autophagy
• human granulosa cells
• anovulation

Disclosure statement

The authors have no conflicts of interest.

Additional information

Funding

This study was supported by the National Natural Science Foundation of China (81571499, 81771648), Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (20161413), National Key R&D Program of China (2017YFC1001403), Program of Shanghai Academic Research Leader in Shanghai Municipal Commission of Health and Family Planning (2017BR015), Clinical Skills Improvement Project of Major Disorders, Hospital Development Center of Shanghai (16CR1022A), and Shanghai Technological Innovation Plan (18140902400).