Huang D, Wei W, Xie F, Zhu X, Zheng L, Lv Z
Department of Histology and Embryology, Anhui Medical University, Hefei, China.
Andrologia. 2018 Feb;50(1). doi: 10.1111/and.12816. Epub 2017 May 9.
To gain an understanding of the mechanisms by which Leydig cell steroidogenic function degenerates with ageing, we explored steroidogenic gene expression in relation to antioxidation status and endoplasmic reticulum (ER) stress during the ageing of mice. Expression of StAR, P450scc and other steroidogenic enzymes decreased starting at middle age (12-month-old) compared to that of the young control (3-month-old) mice. The immunohistochemical staining intensity of 3β-HSD for Leydig cells was significantly weaker in the aged (24-month-old) group than that in the young control group. The number of Leydig cells showed no significant difference between the groups. A progressive reduction in antioxidants MnSOD and GPx4 was observed in the testicular tissue with down-regulated SIRT1 protein level in the middle-aged and aged (24-month-old) mice. The number of testicular macrophages was significantly higher in the aged group than that in the middle-aged and young mice. Age-associated up-regulation of ER stress markers such as GRP78 and Chop was observed. These results suggested that oxidative stress and ER stress might play a role in the deficit of Leydig cell steroidogenic function during ageing.
为了解睾丸间质细胞类固醇生成功能随衰老而退化的机制，我们探讨了小鼠衰老过程中类固醇生成基因表达与抗氧化状态及内质网（ER）应激的关系。与年轻对照组（3个月大）小鼠相比，从中年（12个月大）开始，类固醇生成急性调节蛋白（StAR）、胆固醇侧链裂解酶（P450scc）和其他类固醇生成酶的表达下降。老年组（24个月大）睾丸间质细胞3β-羟基类固醇脱氢酶（3β-HSD）的免疫组化染色强度明显弱于年轻对照组。各组间睾丸间质细胞数量无显著差异。在中年和老年（24个月大）小鼠的睾丸组织中，观察到抗氧化剂锰超氧化物歧化酶（MnSOD）和谷胱甘肽过氧化物酶4（GPx4）逐渐减少，沉默信息调节因子1（SIRT1）蛋白水平下调。老年组睾丸巨噬细胞数量明显高于中年组和年轻小鼠。观察到与年龄相关的内质网应激标志物如葡萄糖调节蛋白78（GRP78）和C/EBP同源蛋白（Chop）上调。这些结果表明，氧化应激和内质网应激可能在衰老过程中睾丸间质细胞类固醇生成功能缺陷中起作用。
