Marinero M J, Penalva V, Oliva J L, Colás B, Prieto J C, López-Ruiz M P
Unidad de Neuroendocrinologia Molecular, Departamento de Bioquímica y Biología Molecular, Universidad de Alcalá, Alcalá de Henares-Madrid, Spain.
FEBS Lett. 1998 Jan 23;422(1):10-4. doi: 10.1016/s0014-5793(97)01584-6.
It is well known that arachidonic acid (AA) acts as an intratesticular factor regulating luteinizing hormone-mediated testicular steroidogenesis. The present studies were conducted to determine the effect of AA on steroidogenic enzymes in rat Leydig cells. Exogenously added AA significantly inhibited 22(R)-hydroxy-cholesterol-stimulated testosterone production, which is a clear indication that AA is acting at some point after cholesterol transport to the inner mitochondrial membrane. AA failed to block the conversion of 22(R)-hydroxycholesterol to pregnenolone, indicating that the cytochrome P-450 side-chain cleavage enzyme complex is not the site of inhibition. The present results demonstrate that only 17beta-hydroxysteroid dehydrogenase seems to be involved in the AA action, since nearly 60% inhibition of testosterone production was found when the cells were incubated with androstenedione. Furthermore, no effect of AA was found when androstenediol was used as substrate in the testosterone synthesis, which indicates that 3beta-hydroxysteroid dehydrogenase is not affected by AA. The conversion of AA to its metabolites is not required for its action on 17beta-hydroxysteroid dehydrogenase and the activation of protein kinase C is not involved in the inhibitory effect.
众所周知，花生四烯酸（AA）作为一种睾丸内因子，可调节促黄体生成素介导的睾丸类固醇生成。本研究旨在确定AA对大鼠睾丸间质细胞类固醇生成酶的影响。外源添加的AA显著抑制了22（R）-羟基胆固醇刺激的睾酮生成，这清楚地表明AA在胆固醇转运至线粒体内膜后的某个环节起作用。AA未能阻断22（R）-羟基胆固醇向孕烯醇酮的转化，表明细胞色素P-450侧链裂解酶复合物不是抑制位点。目前的结果表明，似乎只有17β-羟基类固醇脱氢酶参与了AA的作用，因为当细胞与雄烯二酮一起孵育时，发现睾酮生成受到近60%的抑制。此外，当将雄烯二醇用作睾酮合成的底物时，未发现AA有任何作用，这表明3β-羟基类固醇脱氢酶不受AA影响。AA对17β-羟基类固醇脱氢酶的作用不需要将其转化为代谢产物，且蛋白激酶C的激活不参与这种抑制作用。
