Age-related increase in mitochondrial superoxide generation in the testosterone-producing cells of Brown Norway rat testes: relationship to reduced steroidogenic function?

Age-related increase in mitochondrial superoxide generation in the testosterone-producing cells of Brown Norway rat testes: relationship to reduced steroidogenic function?
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DOI:
10.1016/s0531-5565(01)00118-8
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发表时间:
2001-08-01
影响因子:
3.9
通讯作者:
Zirkin, BR
Zirkin, BR
中科院分区:
医学2区
文献类型:
--
作者:
Chen, HL;Cangello, D;Zirkin, BR

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布朗挪威大鼠的衰老伴随着睾丸间质细胞睾酮产量的减少,睾丸间质细胞负责合成和分泌这种必需的类固醇。到目前为止,间质细胞类固醇合成减少的机制尚不清楚。在此,我们评估生产线粒体活性氧的完整的睾丸间质细胞分离的年轻和老年大鼠。为此,将Leydig细胞与光泽精(bis-N-甲基吖啶鎓)孵育。硝酸盐),一种进入细胞的探针,定位于线粒体,并在与线粒体内超氧化物反应后产生显著的荧光反应。老年大鼠的间质细胞比年轻大鼠的间质细胞引起更大的光泽精衍生的化学发光(LDCL)。电镜体视学分析表明,老年细胞线粒体的绝对体积比年轻细胞减少。这些结果,综合起来,表明,有年龄相关的变化,活性氧的产生由Leydig细胞的线粒体,与老Leydig细胞产生显着更高的水平比年轻的Leydig细胞。这些结果是一致的建议,尿道衍生的活性氧可能发挥作用的不可逆下降的能力,老Leydig细胞产生睾酮。(C)2001 Elsevier Science Inc. All rights reserved.
Aging in Brown Norway rats is accompanied by the reduced production of testosterone by the Leydig cells, the testicular cells responsible for synthesizing and secreting this essential steroid. As yet, the mechanism by which Leydig cell steroidogenesis is reduced is unknown. Herein we assess the production of mitochondrial reactive oxygen species by intact Leydig cells isolated from the testes of young and old rats. To this end, Leydig cells were incubated with lucigenin (bis-N-methylacridinium. nitrate), a probe that enters cells, localizes to mitochondria, and yields a significant chemiluminescent response following its reaction with intramitochondrial superoxide. Leydig cells from old rats elicited significantly greater lucigenin-derived cherniluminescence (LDCL) than those from young rats. Electron microscopic stereological analysis revealed that the absolute volume of mitochondria in the old cells was reduced from that in the young. These results, taken together, suggest that there are age-related changes in the production of reactive oxygen species by the mitochondria of Leydig cells, with those of old Leydig cells producing significantly greater levels than those of young Leydig cells. The results are consistent with the proposal that mitochondrial-derived reactive oxygen may play a role in the irreversible decline in the ability of old Leydig cells to produce testosterone. (C) 2001 Elsevier Science Inc. All rights reserved.