Quinn P G, Georgiou M, Payne A H
Endocrinology. 1985 Jun;116(6):2300-5. doi: 10.1210/endo-116-6-2300.
The metabolism of hydroxysterols, which bypass the cAMP-dependent, cycloheximide-inhibitable transport to cytochrome P-450 side-chain cleavage enzyme complex (P-450scc) required by cholesterol, and whose metabolism exceeds that of cholesterol in luteal cells, has been investigated in primary cultures of Leydig cells purified from the mouse and the rat. An unexpected finding was that metabolism of 25-hydroxycholesterol by mouse Leydig cells was far lower than cAMP-stimulated cholesterol metabolism. The metabolism of 20 alpha-hydroxycholesterol and 22R-hydroxycholesterol was equivalent to and greater than, respectively, maximal cholesterol metabolism by mouse Leydig cells. As expected, metabolism of 25-hydroxycholesterol by rat Leydig cells was much greater than cholesterol metabolism, as was metabolism of 20 alpha-hydroxycholesterol and 22R-hydroxycholesterol. Hydroxysterol metabolism was not increased by cAMP. Cycloheximide abolished the cAMP-stimulated increase in testosterone production by Leydig cells of both species but had no effect on metabolism of any of the hydroxysterols by Leydig cells of either species. In addition, it was shown that the relatively low rate of 25-hydroxycholesterol supported testosterone production in mouse Leydig cells was not due to inhibition of the conversion of pregnenolone to testosterone. It is concluded that a species-specific difference in the control of mitochondrial sterol metabolism exists between the rat and the mouse. The data suggest that either the P-450scc differs between mice and rats or that an effector of P-450scc, which greatly facilitates the binding and metabolism of cholesterol, is of particular importance in the control of sterol metabolism in the mouse Leydig cell.
在从小鼠和大鼠中纯化的睾丸间质细胞原代培养物中，对羟类固醇的代谢进行了研究。羟类固醇的代谢绕过了胆固醇所需的依赖于环磷酸腺苷（cAMP）、受放线菌酮抑制的转运至细胞色素P-450侧链裂解酶复合物（P-450scc）的过程，并且其在黄体细胞中的代谢超过了胆固醇的代谢。一个意外的发现是，小鼠睾丸间质细胞对25-羟胆固醇的代谢远低于cAMP刺激的胆固醇代谢。20α-羟胆固醇和22R-羟胆固醇的代谢分别相当于和大于小鼠睾丸间质细胞的最大胆固醇代谢。正如预期的那样，大鼠睾丸间质细胞对25-羟胆固醇的代谢远大于胆固醇代谢，20α-羟胆固醇和22R-羟胆固醇的代谢也是如此。cAMP并未增加羟类固醇的代谢。放线菌酮消除了两种物种睾丸间质细胞中cAMP刺激的睾酮生成增加，但对两种物种睾丸间质细胞中任何一种羟类固醇的代谢均无影响。此外，研究表明，小鼠睾丸间质细胞中支持睾酮生成的25-羟胆固醇相对较低的代谢率并非由于孕烯醇酮向睾酮转化的抑制。结论是，大鼠和小鼠之间在线粒体固醇代谢控制方面存在物种特异性差异。数据表明，要么小鼠和大鼠的P-450scc不同，要么对P-450scc具有极大促进胆固醇结合和代谢作用的效应器在小鼠睾丸间质细胞的固醇代谢控制中尤为重要。
