FSH and bFGF stimulate the production of glutathione in cultured rat Sertoli cells
FSH and bFGF stimulate the production of glutathione in cultured rat Sertoli cells
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DOI：
10.1111/j.1365-2605.2007.00836.x
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发表时间：
2009-06-01
影响因子：
--
通讯作者：
Schteingart, Helena F.
中科院分区：
文献类型：
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作者：
Gualtieri, Ariel F.;Mazzone, Graciela L.;Schteingart, Helena F.
发育中的生殖细胞从生精上皮的基底室迁移到近腔室需要广泛的组织重组，从而导致活性氧的产生。支持细胞参与了这一过程。由Sertoli细胞产生的谷胱甘肽（GSH）在保护细胞免受氧化应激中具有重要作用。细胞内GSH含量通过从头合成（涉及谷氨酸-半胱氨酸连接酶催化（GCLC）和调节（GCLM）亚基）以及通过谷胱甘肽还原酶（GR）催化的氧化GSH再循环来维持。为了评估促卵泡激素（FSH）和碱性成纤维细胞生长因子（bFGF）是否通过调节GCLC，GCLM和/或GR的表达来调节支持细胞中GSH的产生，我们使用原代培养的大鼠支持细胞进行了体外研究。FSH和bFGF刺激后24小时培养的支持细胞GSH水平增加。FSH和bFGF的同时添加没有产生任何进一步的效果。FSH和bFGF可上调GCLM表达6 h。在24 h时，仅观察到FSH介导的作用。FSH和bFGF也能上调GR的表达。总之，我们的研究结果表明，FSH和bFGF增加GSH水平在支持细胞通过刺激从头合成和回收分别上调GCLM和GR的表达。因此，生殖细胞对氧化应激的保护似乎受到能够影响支持细胞GSH产生的激素和生殖细胞释放的生长因子的调节。
Migration of developing germ cells from the basal to the adluminal compartment of the seminiferous epithelium requires extensive tissue restructuring, resulting in the production of reactive oxygen species. Sertoli cells are involved in this process. Glutathione (GSH), produced by Sertoli cells, has an essential role in cell protection against oxidative stress. Intracellular GSH content is maintained by de novo synthesis, involving glutamate-cysteine ligase catalytic (GCLC) and modulatory (GCLM) subunits, and by recycling from oxidized GSH, catalysed by glutathione reductase (GR). To assess whether follicle-stimulating hormone (FSH) and basic fibroblast growth factor (bFGF) modulate GSH production in Sertoli cells by regulating the expression of GCLC, GCLM and/or GR, we performed in vitro studies using rat Sertoli cells in primary culture. FSH and bFGF stimulation increased Sertoli cell GSH levels after 24 h incubation. The simultaneous addition of FSH and bFGF did not produce any further effect. GCLM expression was upregulated by FSH and bFGF 6 h. At 24 h, only the FSH-mediated effect was still observed. FSH and bFGF also upregulated GR expression. In conclusion, our results show that FSH and bFGF increase GSH levels in Sertoli cells through stimulation of the de novo synthesis and recycling by upregulating GCLM and GR expression respectively. Therefore, protection of germ cells against oxidative stress seems to be regulated by hormones and germ cell-released growth factors capable of influencing the production of Sertoli cell GSH.