Testosterone modulates K+ATP Channels in Sertoli cell membrane via the PLC-PIP2 pathway
Testosterone modulates K+ATP Channels in Sertoli cell membrane via the PLC-PIP2 pathway
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DOI：
10.1055/s-2004-825753
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发表时间：
2004-08-01
影响因子：
2.2
通讯作者：
Wassermann, GF
中科院分区：
文献类型：
--
作者：
Loss, ES;Jacobsen, M;Wassermann, GF
睾丸内生理浓度的睾酮可引起剂量依赖性的去极化和输入阻力的增加，并增加未成熟大鼠曲细精管支持细胞对Ca-45（2+）的摄取。以前的研究表明K-ATP（+）通道参与了这些睾酮的作用。本研究表明，睾酮和磺脲类药物（格列本脲和甲苯磺丁脲）使10 - 15日龄大鼠生精小管支持细胞膜电位去极化，增加阻力和Ca-45（2+）摄取。这些作用被K-ATP（+）通道开放剂二氮嗪的存在所抵消。用不渗透的牛血清白蛋白结合睾酮也观察到去极化。睾酮作用被百日咳毒素和磷脂酶C（PLC）抑制剂U 73122阻断，这意味着PLC -磷脂酰肌醇4-5二磷酸（PIP 2）通过G蛋白水解参与睾酮作用。聚阳离子，包括精胺和氯化镧，去极化的膜电位，并增加了电阻。EGTA引起的超极化被LaCl 3和睾酮逆转。最后一种效应由于U 73122的存在而无效。所有上述结果表明，睾酮对支持细胞膜的作用通过PLC-PIP 2水解作用于K-ATP（+）通道，该水解作用关闭通道，使膜去极化，并刺激Ca-45（2+）摄取。
Testosterone at physiological intratesticular concentrations induces a dose-dependent depolarisation and an increase in input resistance together with an increment of Ca-45(2+) uptake in the Sertoli cells from seminiferous tubules of immature rat. Previous studies have implicated K-ATP(+) channels in these testosterone actions. This study demonstrates that testosterone and sulphonylureas (glibenclamide and tolbutamide) depolarise the membrane potential, augment resistance and Ca-45(2+) uptake in the Sertoli cells of seminiferous tubules from 10 - 15 day-old rats. These actions were nullified by the presence of the K-ATP(+) channel opener diazoxide. The depolarisation was also observed with the impermeant bovine serum albumin-bound testosterone. Testosterone actions were blocked by both pertussis toxin and the phospholipase C (PLC) inhibitor U73122 implying the involvement of PLC - phosphatidylinositol 4-5 bisphosphate (PIP2) hydrolysis via G protein in testosterone actions. Polycations, including spermine and LaCl3, depolarised the membrane potential and increased the resistance. Hyperpolarisation caused by EGTA was reversed by LaCl3 and by the presence of testosterone. This last effect was nullified by the presence of U73122. All of the above results indicate that the action of testosterone on the Sertoli cell membrane is exercised on the K-ATP(+) channels through PLC-PIP2 hydrolysis that closes the channel, depolarises the membrane, and stimulates Ca-45(2+) uptake.