Gualtieri Ariel F, Mazzone Graciela L, Rey Rodolfo A, Schteingart Helena F
Centro de Investigaciones Endocrinológicas (CEDIE-CONICET), Hospital de Niños R. Gutiérrez, Buenos Aires, Argentina.
Int J Androl. 2009 Jun;32(3):218-25. doi: 10.1111/j.1365-2605.2007.00836.x. Epub 2007 Nov 27.
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.
发育中的生殖细胞从生精上皮的基底部分迁移到近腔部分需要广泛的组织重构，这会产生活性氧。支持细胞参与了这一过程。支持细胞产生的谷胱甘肽（GSH）在细胞抵御氧化应激中起着至关重要的作用。细胞内GSH含量通过从头合成来维持，这涉及谷氨酸 - 半胱氨酸连接酶催化亚基（GCLC）和调节亚基（GCLM），还通过谷胱甘肽还原酶（GR）催化的氧化型GSH循环利用来维持。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。孵育24小时后，FSH和bFGF刺激增加了支持细胞的GSH水平。同时添加FSH和bFGF没有产生进一步的影响。FSH和bFGF在6小时时上调了GCLM的表达。在24小时时，仅观察到FSH介导的效应。FSH和bFGF也上调了GR的表达。总之，我们的结果表明，FSH和bFGF通过分别上调GCLM和GR的表达来刺激从头合成和循环利用，从而增加支持细胞中的GSH水平。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。
