Leydig cell aging and hypogonadism.
Leydig cell aging and hypogonadism.
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DOI：
10.1016/j.exger.2015.02.014
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发表时间：
2015-08
影响因子：
3.9
通讯作者：
Zirkin BR
中科院分区：
文献类型：
--
作者：
Beattie MC;Adekola L;Papadopoulos V;Chen H;Zirkin BR
间质细胞睾酮 (T) 的产生随着年龄的增长而减少，导致血清 T 水平降低（性腺功能减退症）。在衰老的 Leydig 细胞的类固醇生成途径中发现了许多与 T 形成减少相关的细胞变化，包括黄体生成素 (LH) 刺激的 cAMP 产生、胆固醇转运蛋白类固醇生成急性调节 (STAR) 蛋白和易位蛋白 (TSPO) 以及线粒体和平滑内质网的下游类固醇生成酶的减少。年轻细胞氧化还原环境的实验改变可以引起衰老间质细胞特征性的类固醇形成的许多变化，这表明细胞内氧化还原平衡的变化可能导致 T 产生减少。据估计，性腺功能减退症影响着大约 500 万美国男性，包括老年人和年轻人。这种情况与情绪变化、认知能力恶化、疲劳、抑郁、去脂体重减少、骨矿物质密度降低、内脏脂肪增加、代谢综合征、性欲下降和性功能障碍有关。外源 T 给药现在广泛用于提高性腺功能减退男性的血清 T 水平，从而治疗性腺功能减退症的症状。然而，最近的证据表明，服用外源 T 的男性可能面临中风、心脏病和前列腺肿瘤发生的风险增加。此外，众所周知，施用 T 可对 LH 产生抑制作用，导致 Leydig 细胞 T 生成减少、睾丸内 T 浓度降低和精子发生减少。这使得外源 T 给药不适合想要生育孩子的男性。有前景的新方法可以通过直接刺激 Leydig 细胞 T 产生而不是通过外源 T 疗法来增加血清 T，从而有可能避免其一些负面后果。
Leydig cell testosterone (T) production is reduced with age, resulting in reduced serum T levels (hypogonadism). A number of cellular changes have been identified in the steroidogenic pathway of aged Leydig cells that are associated with reduced T formation, including reductions in luteinizing hormone (LH)-stimulated cAMP production, the cholesterol transport proteins steroidogenic acute regulatory (STAR) protein and translocator protein (TSPO), and downstream steroidogenic enzymes of the mitochondria and smooth endoplasmic reticulum. Many of the changes in steroid formation that characterize aged Leydig cells can be elicited by the experimental alteration of the redox environment of young cells, suggesting that changes in the intracellular redox balance may cause reduced T production. Hypogonadism is estimated to affect about 5 million American men, including both aged and young. This condition has been linked to mood changes, worsening cognition, fatigue, depression, decreased lean body mass, reduced bone mineral density, increased visceral fat, metabolic syndrome, decreased libido, and sexual dysfunction. Exogenous T administration is now used widely to elevate serum T levels in hypogonadal men and thus to treat symptoms of hypogonadism. However, recent evidence suggests that men who take exogenous T may face increased risk of stroke, heart attack, and prostate tumorigenesis. Moreover, it is well established that administered T can have suppressive effects on LH, resulting in lower Leydig cell T production, reduced intratesticular T concentration, and reduced spermatogenesis. This makes exogenous T administration inappropriate for men who wish to father children. There are promising new approaches to increase serum T by directly stimulating Leydig cell T production rather than by exogenous T therapy, thus potentially avoiding some of its negative consequences.
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影响因子：
3.7
作者：
Finkle WD;Greenland S;Ridgeway GK;Adams JL;Frasco MA;Cook MB;Fraumeni JF Jr;Hoover RN
通讯作者：
Hoover RN
影响因子：
--
作者：
Bobjer, J.;Naumovska, M.;Giwercman, A.
通讯作者：
Giwercman, A.
影响因子：
4.8
作者：
Bosland, Maarten C.
通讯作者：
Bosland, Maarten C.
DOI：
10.1111/j.1749-6632.2002.tb02084.x
发表时间：
2002-01-01
期刊：
INCREASING HEALTHY LIFE SPAN: CONVENTIONAL MEASURES AND SLOWING THE INNATE AGING PROCESS
影响因子：
--
作者：
Drew, B;Leeuwenburgh, C
通讯作者：
Leeuwenburgh, C
影响因子：
3.9
作者：
Chen, HL;Cangello, D;Zirkin, BR
通讯作者：
Zirkin, BR