Luteinizing hormone stimulates the expression of amphiregulin in human theca cells

Journal of Ovarian Research

Research

Xi Guo¹  Turui Yang¹  Xiaoting Shen¹  Minghui Chen¹  Yiping Zhong¹  Rihan Wu¹  Yang Liu² 

[1] Reproductive Medicine Center, The First Affiliated Hospital of Sun Yat-sen University, Zhoushan 2 Road, Guangzhou, Guangdong, People’s Republic of China;Guangdong Provincial Key Laboratory of Reproductive Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China;Reproductive Medicine Center, The First Affiliated Hospital of Sun Yat-sen University, Zhoushan 2 Road, Guangzhou, Guangdong, People’s Republic of China;Guangdong Provincial Key Laboratory of Reproductive Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China;Obstetrics and Gynaecology Hospital of Fudan University, Shanghai, China;

关键词: Amphiregulin;    Theca cells;    Granulosa cells;    Luteinizing hormone;    cAMP/PKA signalling pathway;   

DOI  :  10.1186/s13048-022-01062-5

 received in 2022-06-27, accepted in 2022-11-20,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundLuteinizing hormone (LH) can stimulate mural granulosa cells to produce Amphiregulin (AREG), which can induce the resumption of meiosis in oocytes. Theca cells are present in the outer layer of follicles, providing communication with the pituitary axis through the established vascular system around the follicle. As LH target cells, it is unknown whether theca cells can produce AREG after LH stimulation.MethodsPrimary cultured human theca cells were treated with LH (with or without the inhibitor of PKA, H89), or agonists of adenylate cyclase (forskolin or db-cAMP). The mRNA and protein levels of AREG were evaluated by RT-qPCR, immunochemistry, immunofluorescence, western blotting, and ELISA.ResultsImmunohistochemistry of normal ovarian tissue obtained in the early-mid follicle phase showed that AREG expression was absent in both the theca layer and the granulosa cell layer of antral follicles. Double immunofluorescent staining revealed colocalization of AREG and CYP17A1 in human theca cells and colocalization of FSHR and AREG in human granulosa cells isolated from follicular fluid collected during IVF/ICSI after hCG trigger. LH significantly increased the mRNA and protein levels of AREG in human theca cells and the concentration of AREG in the culture medium. Forskolin and db-cAMP, activators of the cAMP/PKA signalling pathway, also significantly increased the mRNA and protein levels of AREG in human theca cells and the concentration of AREG in the culture medium. H89 antagonized the stimulating effect of LH on AREG expression in human theca cells. In addition, the concentration of AREG was lower in polycystic ovarian syndrome (PCOS) follicular fluid than in normal follicular fluid. The mRNA levels of AREG were significantly lower in PCOS granulosa cells and theca cells than in normal granulosa cells and theca cells.ConclusionLH can stimulate the expression of AREG in human theca cells, and the adenylate cyclase/cAMP/PKA cascade may mediate this process. Expression of AREG is decreased in PCOS theca cells compared to normal theca cells, with or without LH stimulation.

【 授权许可】

CC BY   
© The Author(s) 2022

【 图 表 】

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