Development and function of the adult generation of Leydig cells in mice with sertoli cell-selective or total ablation of the androgen receptor
Development and function of the adult generation of Leydig cells in mice with sertoli cell-selective or total ablation of the androgen receptor
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DOI：
10.1210/en.2005-0300
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发表时间：
2005-09-01
期刊：
影响因子：
4.8
通讯作者：
Verhoeven, G
中科院分区：
文献类型：
--
作者：
De Gendt, K;Atanassova, N;Verhoeven, G
雄激素和未识别的支持细胞（SC）衍生因子可影响啮齿动物成体间质细胞（LC）的发育，但其机制尚不清楚。我们评估了sc选择性雄激素受体（AR）敲除（SCARKO）和AR完全敲除（ARKO）小鼠成年LC的发育和功能。在对照组中，在12至140日龄之间，LC数量增加了26倍，LC大小增加了约2倍。SCARKOs的LC数量在12 d时正常，但随着年龄的增长，LC数量减少了40%以上，尽管到成年时LC比对照LC更大，含有更多的脂滴和线粒体。与对照组相比，各年龄段的ARKO LC数量减少了83%，LC大小在12 d后没有增加。成人scarko和对照组的血清LH和睾酮水平和精囊重量相当，而arko患者的LH水平升高了8倍，尽管睾酮水平正常。免疫组织化学和LC特异性标记的定量PCR显示，每个LC的类固醇生成功能可能在SCARKOs中增加而在ARKOs中减少。在SCARKOs中，胰岛素样因子-3和雌激素硫转移酶（estrogen sulfate transferase， EST） mRNA的表达与对照组相比没有变化，分别增加了3倍，而在ARKOs中，两者的表达均降低了90%以上。EST表达的改变，加上血小板衍生生长因子- a表达的减少，是SCARKOs中LC数量和功能改变的潜在原因。这些结果表明，SC上雄激素作用的丧失对LC的发展有重要影响，这可能通过血小板衍生生长因子- a和/或雌激素/EST间接介导。
It is established that androgens and unidentified Sertoli cell (SC)-derived factors can influence the development of adult Leydig cells (LC) in rodents, but the mechanisms are unclear. We evaluated adult LC development and function in SC-selective androgen receptor (AR) knockout (SCARKO) and complete AR knockout (ARKO) mice. In controls, LC number increased 26-fold and LC size increased by approximately 2-fold between 12 and 140 d of age. LC number in SCARKOs was normal on d 12, but was reduced by more than 40% at later ages, although LC were larger and contained more lipid droplets and mitochondria than control LC by adulthood. ARKO LC number was reduced by up to 83% at all ages compared with controls, and LC size did not increase beyond d 12. Serum LH and testosterone levels and seminal vesicle weights were comparable in adult SCARKOs and controls, whereas LH levels were elevated 8-fold in ARKOs, although testosterone levels appeared normal. Immunohistochemistry and quantitative PCR for LC-specific markers indicated steroidogenic function per LC was probably increased in SCARKOs and reduced in ARKOs. In SCARKOs, insulin-like factor-3 and estrogen sulfotransferase (EST) mRNA expression were unchanged and increased 3-fold, respectively, compared with controls, whereas the expression of both was reduced more than 90% in ARKOs. Changes in EST expression, coupled with reduced platelet-derived growth factor-A expression, are potential causes of altered LC number and function in SCARKOs. These results show that loss of androgen action on SC has major consequences for LC development, and this could be mediated indirectly via platelet-derived growth factor-A and/or estrogens/EST.