Igarashi Y, Kimura T
J Biol Chem. 1984 Sep 10;259(17):10745-53.
We examined the subcellular localization of ACTH (adrenocorticotropic hormone)-induced changes in adrenal phospholipids using dexamethasone-treated rats. In adrenal mitochondrial fraction, ACTH significantly enhanced both concentrations and contents of phosphatidylinositol (37%), phosphatidylcholine (22%), and phosphatidylethanolamine (20%). Other mitochondrial phospholipids including cardiolipin did not change upon administration of ACTH. In adrenal plasma membrane, endoplasmic reticulum, and peroxisomes, no increase in phospholipids was observed. The ACTH-induced increases in mitochondrial phosphatidylinositol, phosphatidylcholine, and phosphatidylethanolamine were specific to adrenal among tissues tested. These changes were observed specifically in cortical cells rather than medulla. Nonsteroidogenic ACTH fragments and related peptides were unable to induce the change in adrenal mitochondrial phospholipids. From the dose-response profile with ACTH, the changes in mitochondrial phospholipids were closely related to ACTH-dependent stimulation of steroidogenesis. Furthermore, in vitro treatment with cyclic AMP enhanced both concentrations and contents of mitochondrial phosphatidylinositol, phosphatidylcholine, and phosphatidylethanolamine similar to those by the in vivo administration of ACTH. Both in vivo and in vitro experiments revealed that the hormone-induced changes in mitochondrial phospholipids were sensitive to a protein-synthesis inhibitor, cycloheximide. However, aminoglutethimide and cytochalasin B, which strongly inhibited the hormone-induced formation of corticosterone, did not affect the increases in mitochondrial phospholipids. These results suggest that the hormone-induced increases in these phospholipids occur between ACTH-mediated ribosomal protein synthesis and corticosterone formation.
我们使用地塞米松处理的大鼠研究了促肾上腺皮质激素（ACTH）诱导的肾上腺磷脂亚细胞定位变化。在肾上腺线粒体部分，ACTH显著提高了磷脂酰肌醇（37%）、磷脂酰胆碱（22%）和磷脂酰乙醇胺（20%）的浓度和含量。包括心磷脂在内的其他线粒体磷脂在给予ACTH后没有变化。在肾上腺质膜、内质网和过氧化物酶体中，未观察到磷脂增加。ACTH诱导的线粒体磷脂酰肌醇、磷脂酰胆碱和磷脂酰乙醇胺增加在测试组织中对肾上腺具有特异性。这些变化特异性地出现在皮质细胞而非髓质中。非甾体生成性ACTH片段和相关肽无法诱导肾上腺线粒体磷脂的变化。从ACTH的剂量反应曲线来看，线粒体磷脂的变化与ACTH依赖性的类固醇生成刺激密切相关。此外，用环磷酸腺苷进行体外处理可提高线粒体磷脂酰肌醇、磷脂酰胆碱和磷脂酰乙醇胺的浓度和含量，类似于体内给予ACTH的情况。体内和体外实验均表明，激素诱导的线粒体磷脂变化对蛋白质合成抑制剂环己酰亚胺敏感。然而，强烈抑制激素诱导的皮质酮形成的氨鲁米特和细胞松弛素B并不影响线粒体磷脂的增加。这些结果表明，激素诱导的这些磷脂增加发生在ACTH介导的核糖体蛋白合成和皮质酮形成之间。
