Bollag Wendy B, Kent Patricia, White Stephanie, Wilson Mariya V, Isales Carlos M, Calle Roberto A
Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA 30912, USA.
Mol Cell Endocrinol. 2008 Dec 16;296(1-2):53-7. doi: 10.1016/j.mce.2008.08.022. Epub 2008 Aug 28.
The first step in steroidogenesis is cholesterol mobilization from cytosolic lipid droplets to the initiating rate-limiting enzyme complex located on the inner mitochondrial membrane. Angiotensin II (AngII), the primary agonist of aldosterone secretion from adrenal glomerulosa cells, is known to induce cholesterol mobilization to mitochondria. However, the role of the protein kinase C (PKC) pathway in mediating cholesterol mobilization is unknown. To determine PKC's involvement, human adrenocortical carcinoma cells were incubated with or without PKC-activating phorbol 12-myristate 13-acetate (PMA) and mitochondrial cholesterol content assayed. Like AngII, PMA significantly elevated mitochondrial cholesterol content as well as aldosterone secretion. Thus, PKC may play a role in cholesterol mobilization to mitochondria and hence steroid production. Atrial natriuretic peptide (ANP) inhibited both AngII- and PMA-stimulated mitochondrial cholesterol content. These findings suggest that the ability of ANP to inhibit steroidogenesis induced by multiple agents may be related to its capacity to reduce cholesterol mobilization.
类固醇生成的第一步是将胆固醇从胞质脂质小滴转运至位于线粒体内膜的起始限速酶复合物。血管紧张素II（AngII）是肾上腺球状带细胞分泌醛固酮的主要激动剂，已知其可诱导胆固醇转运至线粒体。然而，蛋白激酶C（PKC）途径在介导胆固醇转运中的作用尚不清楚。为确定PKC的参与情况，将人肾上腺皮质癌细胞与PKC激活剂佛波酯12-肉豆蔻酸酯13-乙酸酯（PMA）一起孵育或不孵育，然后检测线粒体胆固醇含量。与AngII一样，PMA显著提高了线粒体胆固醇含量以及醛固酮分泌。因此，PKC可能在胆固醇转运至线粒体从而参与类固醇生成过程中发挥作用。心房利钠肽（ANP）抑制了AngII和PMA刺激的线粒体胆固醇含量。这些发现表明，ANP抑制多种因子诱导的类固醇生成的能力可能与其降低胆固醇转运的能力有关。
