Role and mechanism of AMH in the regulation of Sertoli cells in mice

Role and mechanism of AMH in the regulation of Sertoli cells in mice
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AMH在小鼠支持细胞调节中的作用及机制

DOI:
10.1016/j.jsbmb.2017.08.011
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发表时间:
2017-11
影响因子:
4.1
通讯作者:
Yang Liguo
Yang Liguo
中科院分区:
生物学2区
文献类型:
--
作者:
Rehman Zia Ur;Worku Tesfaye;Davis John S.;Talpur Hira Sajjad;Bhattarai Dinesh;Kadariya Ishwari;Hua Guohua;Cao Jing;Dad Rahim;Farmanullah;Hussain Tarique;Yang Liguo

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支持细胞产生抗苗勒氏管激素 (AMH),这是一种属于转化生长因子-β 家族的糖蛋白。 AMH 介导发育中男性胎儿苗勒氏管的退化。然而,AMH 在调节原代支持细胞中的作用仍不清楚。本研究旨在研究 AMH 对支持细胞活力和增殖的影响,特别关注干细胞因子 (SCF)。用浓度不断增加的 rh-AMH(0、10、50、100 和 800 ng/ml)处理支持细胞两天,结果表明,高浓度的 AMH 会增加细胞凋亡。 Caspase-3 和 Bax 的显着增加以及 Bcl-2 蛋白和 mRNA 表达的减少证实了这些结果 (P < 0.01)。矛盾的是,低浓度的 rh-AMH (10 ng/ml),而不是高浓度 (50–800 ng/ml) 的治疗,促进了支持细胞增殖,PCNAmRNA 的增加证实了这一点 (P < 0.05)。此外,只有低浓度的 rh-AMH 才能激活非经典 ERK 信号通路。同样,低浓度的 rh-AMH (10–50 ng/ml) 显着增加 (P < 0.05)SCFmRNA 和 SCF 蛋白水平。这些发现表明,AMH 通过在低浓度下促进增殖和在高浓度下促进细胞凋亡来差异性地调节支持细胞的命运。此外,AMH 还增加了 SCF 的表达,SCF 是支持细胞发育的重要调节因子。因此,AMH 可能在支持细胞发育中发挥作用。
Sertoli cells produce anti-Müllerian hormone (AMH), a glycoprotein belonging to the transforming growth factor-beta family. AMH mediates the regression of Müllerian ducts in the developing male fetus. However, the role of AMH in the regulation of primary Sertoli cells remains unclear. The present study was designed to investigate the effect of AMH on the viability and proliferation of Sertoli cells, with an additional focus on stem cell factor (SCF). Treatment of Sertoli cells with increasing concentrations of rh-AMH (0, 10, 50, 100, and 800 ng/ml) for two days revealed that AMH, at high concentrations, increased apoptosis. These results were confirmed by a significant increase in Caspase-3 and Bax and a decrease in Bcl-2 protein and mRNA expression (P < 0.01). Paradoxically, treatment with a low concentration of rh-AMH (10 ng/ml), but not higher concentrations (50–800 ng/ml), promoted Sertoli cell proliferation, which was verified by an increase inPCNAmRNA (P < 0.05). Furthermore, only low concentrations of rh-AMH activated the non-canonical ERK signaling pathway. Similarly, low concentrations of rh-AMH (10–50 ng/ml) significantly increased (P < 0.05)SCFmRNA and SCF protein levels. These findings indicate that AMH differentially regulates the fate of Sertoli cellsin vitroby promoting proliferation at low concentrations and apoptosis at high concentrations. In addition, AMH increased the expression of SCF, an important regulator of Sertoli cell development. Therefore, AMH may play a role in Sertoli cell development.
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