Tu Lan N, Zhao Amy H, Stocco Douglas M, Selvaraj Vimal
Department of Animal Science, College of Agriculture and Life Sciences (L.N.T., A.H.Z., V.S.), Cornell University, Ithaca, New York 14853; and Department of Cell Biology and Biochemistry, School of Medicine (D.M.S.), Texas Tech University Health Sciences Center, Lubbock, Texas 79430.
Endocrinology. 2015 Mar;156(3):1033-9. doi: 10.1210/en.2014-1707. Epub 2014 Dec 23.
Translocator protein (TSPO) is a mitochondrial outer membrane protein of unknown function with high physiological expression in steroidogenic cells. Using TSPO gene-deleted mice, we recently demonstrated that TSPO function is not essential for steroidogenesis. The first link between TSPO and steroidogenesis was established in studies showing modest increases in progesterone production by adrenocortical and Leydig tumor cell lines after treatment with PK11195. To reconcile discrepancies between physiological and pharmacological interpretations of TSPO function, we generated TSPO-knockout MA-10 mouse Leydig tumor cells (MA-10:TspoΔ/Δ) and examined their steroidogenic potential after exposure to either dibutyryl-cAMP or PK11195. Progesterone production in MA-10:TspoΔ/Δ after dibutyryl-cAMP was not different from control MA-10:Tspo+/+ cells, confirming that TSPO function is not essential for steroidogenesis. Interestingly, when treated with increasing concentrations of PK11195, both control MA-10:Tspo+/+ cells and MA-10:TspoΔ/Δ cells responded in a similar dose-dependent manner showing increases in progesterone production. These results show that the pharmacological effect of PK11195 on steroidogenesis is not mediated through TSPO.
转位蛋白（TSPO）是一种线粒体外膜蛋白，功能未知，在类固醇生成细胞中具有高生理表达。利用TSPO基因敲除小鼠，我们最近证明TSPO功能对于类固醇生成并非必不可少。TSPO与类固醇生成之间的第一个联系是在研究中建立的，这些研究表明，用PK11195处理后，肾上腺皮质和睾丸间质肿瘤细胞系的孕酮产量有适度增加。为了协调对TSPO功能的生理学和药理学解释之间的差异，我们构建了TSPO基因敲除的MA-10小鼠睾丸间质肿瘤细胞（MA-10:TspoΔ/Δ），并在暴露于二丁酰环磷腺苷（dibutyryl-cAMP）或PK11195后检测它们的类固醇生成潜力。二丁酰环磷腺苷处理后，MA-10:TspoΔ/Δ中的孕酮产量与对照MA-10:Tspo+/+细胞没有差异，证实TSPO功能对于类固醇生成并非必不可少。有趣的是，当用浓度递增的PK11195处理时，对照MA-10:Tspo+/+细胞和MA-10:TspoΔ/Δ细胞均以相似的剂量依赖性方式作出反应，孕酮产量增加。这些结果表明，PK11195对类固醇生成的药理作用不是通过TSPO介导的。
