Sun Yan, Yang WeiRong, Luo HongLin, Wang XianZhong, Chen ZhongQiong, Zhang JiaoJiao, Wang Yi, Li XiaoMin
College of Animal Science and Technology, Southwest University, Beibei, Chongqing, PR China; ChongQing Animal Disease Prevention and Control Center, YuBei, ChongQing, PR China.
College of Animal Science and Technology, Southwest University, Beibei, Chongqing, PR China.
Theriogenology. 2015 Jan 1;83(1):86-94. doi: 10.1016/j.theriogenology.2014.08.003. Epub 2014 Aug 10.
Accumulating researches show that thyroid hormone (TH) inhibits Sertoli cells (SCs) proliferation and stimulates their functional maturation in prepubertal rat testis, confirming that TH plays a key role in testicular development. However, the mechanism under the T3 regulation of piglet SC proliferation remains unclear. In the present study, in order to investigate the possible mechanism of T3 on the suppression of SC proliferation, the expression pattern of TRα1 and cell cycle-related molecules, effect of T3 on SC proliferation, and the role of phosphoinositide 3-kinase (PI3K)/Akt signaling pathway on the T3-mediated SC proliferation in piglet testis were explored. Our results demonstrated that TRα1 was expressed in all tested stages of SCs and decreased along with the ages. T3 inhibited the proliferation of SCs in a time- and dose-dependent manner, and T3 treatment downregulated the expressions of cell cycling molecules, such as cyclinA2, cyclinD1, cyclinE1, PCNA, and Skp2, but upregulated the p27 expression in SCs. Most importantly, the suppressive effects of T3 on SC proliferation seemed dependent on the inhibition of PI3K/Akt signaling pathway, and pre-stimulation of PI3K could enhance such suppressive effects. Together, our findings demonstrate that TH inhibits the proliferation of piglet SCs via the suppression of PI3K/Akt signaling pathway.
越来越多的研究表明，甲状腺激素（TH）在青春期前大鼠睾丸中可抑制支持细胞（SCs）增殖并刺激其功能成熟，这证实了TH在睾丸发育中起关键作用。然而，T3调控仔猪支持细胞增殖的机制仍不清楚。在本研究中，为了探究T3抑制支持细胞增殖的可能机制，我们研究了TRα1和细胞周期相关分子的表达模式、T3对支持细胞增殖的影响，以及磷酸肌醇3激酶（PI3K）/Akt信号通路在T3介导的仔猪睾丸支持细胞增殖中的作用。我们的结果表明，TRα1在支持细胞的所有测试阶段均有表达，并随年龄增长而降低。T3以时间和剂量依赖性方式抑制支持细胞增殖，T3处理下调了细胞周期分子如细胞周期蛋白A2、细胞周期蛋白D1、细胞周期蛋白E1、增殖细胞核抗原（PCNA）和Skp2的表达，但上调了支持细胞中p27的表达。最重要的是，T3对支持细胞增殖的抑制作用似乎依赖于对PI3K/Akt信号通路的抑制，PI3K的预刺激可增强这种抑制作用。总之，我们的研究结果表明，TH通过抑制PI3K/Akt信号通路来抑制仔猪支持细胞的增殖。
