Alteration in reproductive hormones profile is associated with the increasing risk of menopausal depression in women. Serum follicle-stimulating hormone (FSH) level is changed during the menopause transition, while the effect of FSH on menopausal depression has remained undefined. In this study we investigated whether or how FSH affected menopausal depression in postmenopausal (ovariectomized) FSHR knockout mice (Fshr^−/−). We found that Fshr^−/− mice displayed aggravated depression-like behaviors, accompanied by severe oxidative stress in the whole brain, resulted from significantly reduced glutamate cysteine ligase modifier subunit (GCLm) in glutathione synthesis and glucose-6-phosphate dehydrogenase (G6PD) in NADP/NADPH transition. Importantly, administration of ROS scavenger N-acetyl cysteine (NAC, 150 mg · kg⁻¹ · d⁻¹, i.p. for 12 weeks) attenuated the depression-like behaviors of Fshr^−/− mice. Consistent with these in vivo experiment results, we found that pretreatment with FSH (50, 100 ng/mL) dose-dependently increased protein levels of GCLm and G6PD, and decreased the ROS production in N2a mouse neuroblastoma cells. These findings demonstrate that FSH signaling is involved in pathogenesis of menopausal depression, and likely to maintain the redox-optimized ROS balance in neurons.

生殖激素谱的改变与妇女绝经期抑郁症的风险增加有关。在更年期过渡期间，血清促卵泡激素（FSH）水平发生了变化，而FSH对更年期抑郁症的影响仍未确定。在这项研究中，我们调查了FSH是否或如何影响绝经后（去卵巢的）FSHR基因敲除小鼠（Fshr ^{-/ -}）的绝经抑郁症。我们发现Fshr ^-/-小鼠表现出严重的抑郁样行为，并伴随着全脑严重的氧化应激，这是由于谷胱甘肽合成中的谷氨酸半胱氨酸连接酶修饰子亚基（GCLm）显着减少和NADP / NADPH过渡中的葡萄糖-6-磷酸脱氢酶（G6PD）引起的。重要的是，服用ROS清除剂N-乙酰半胱氨酸（NAC，150 mg·kg ^-1  ·d ^-1，腹腔注射12周）可减轻Fshr ^{-/ -}的抑郁样行为。老鼠。与这些体内实验结果一致，我们发现用FSH（50，100 ng / mL）进行预处理可以剂量依赖性地增加GCLm和G6PD的蛋白质水平，并减少N2a小鼠神经母细胞瘤细胞中的ROS产生。这些发现表明FSH信号参与更年期抑郁症的发病机理，并可能维持神经元中氧化还原优化的ROS平衡。