Yanase T, Hara T, Sakai Y, Takayanagi R, Nawata H
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Eur J Endocrinol. 1996 Apr;134(4):501-7. doi: 10.1530/eje.0.1340501.
Sterol carrier protein 2 (SCP2) has been implicated in adrenal steroidogenesis by in vitro studies. In order to clarify the clinical significance of SCP2 in human steroidogenesis, we investigated the expression of SCP2 mRNA in various types of adrenocortical tissue and one testis and examined the correlation between the amounts of SCP2 and other values such as the free cholesterol content and the cholesterol side-chain cleavage (SCC) activity in the tissue mitochondria. The types of adrenocortical tissue examined included adrenocortical carcinomas (N = 3), adrenocortical adenomas from patients with Conn's syndrome (N = 3) and from patients with Cushing's syndrome (N = 3), non-functioning adrenocortical adenomas (N = 2) and normal adrenal glands (N = 2). Northern blot hybridization predominantly revealed a 1.8-kb SCP2 mRNA in all tissue specimens examined. The mRNA concentrations of SCP2 in two out of three adrenocortical carcinomas were relatively lower than those in other types of tissue. No other special tendency was observed regarding the mRNA expression levels in various tissue specimens. The mRNA concentrations of SCP2 correlated significantly with mitochondrial contents of free cholesterol (r = 0.67, p < 0.01), but was not correlated with the SCC activities in mitochondria measured by an in vitro enzyme assay. The mitochondrial SCC activities, however, were correlated significantly with the protein levels of mitochondrial P-450 scc determined by a Western blot analysis (r = 0.79, p < 0.01). The significant positive correlation between mRNA concentrations of SCP2 and the mitochondrial content of free cholesterol suggests that the central role of SCP2 in human steroidogenic tissues may be in part a translocation of cytoplasmic free cholesterol to the mitochondria, as demonstrated previously by in vitro studies.
体外研究表明,固醇载体蛋白2(SCP2)与肾上腺类固醇生成有关。为了阐明SCP2在人类类固醇生成中的临床意义,我们研究了SCP2 mRNA在各种类型肾上腺皮质组织及一个睾丸中的表达,并检测了SCP2含量与其他指标(如组织线粒体中游离胆固醇含量和胆固醇侧链裂解酶(SCC)活性)之间的相关性。所检测的肾上腺皮质组织类型包括肾上腺皮质癌(n = 3)、原发性醛固酮增多症患者的肾上腺皮质腺瘤(n = 3)、库欣综合征患者的肾上腺皮质腺瘤(n = 3)、无功能肾上腺皮质腺瘤(n = 2)和正常肾上腺(n = 2)。Northern印迹杂交显示,在所检测的所有组织标本中,主要出现一条1.8 kb的SCP2 mRNA条带。在3例肾上腺皮质癌中,有2例的SCP2 mRNA浓度相对低于其他类型组织。在各种组织标本的mRNA表达水平上未观察到其他特殊趋势。SCP2的mRNA浓度与线粒体游离胆固醇含量显著相关(r = 0.67,p < 0.01),但与体外酶法检测的线粒体SCC活性无关。然而,线粒体SCC活性与Western印迹分析测定的线粒体P-450 scc蛋白水平显著相关(r = 0.79,p < 0.01)。SCP2的mRNA浓度与线粒体游离胆固醇含量之间的显著正相关表明,SCP2在人类类固醇生成组织中的核心作用可能部分在于将细胞质中的游离胆固醇转运至线粒体,这正如先前体外研究所证明的那样。