Expression of Ovary-Specific Acidic Protein in Steroidogenic Tissues: A Possible Role in Steroidogenesis
Expression of Ovary-Specific Acidic Protein in Steroidogenic Tissues: A Possible Role in Steroidogenesis
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DOI：
10.1210/en.2008-1584
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发表时间：
2009-07-01
期刊：
影响因子：
4.8
通讯作者：
Yoshimura, Yasunori
中科院分区：
文献类型：
--
作者：
Matsumoto, Tadashi;Minegishi, Kazuhiro;Yoshimura, Yasunori
卵巢特异性酸性蛋白（OSAP）是从旨在识别小鼠卵巢选择性基因的基因组计划中发现的一种新型分子。尽管公共数据库提示OSAP在卵巢外表达，但其组织分布尚未得到很好的记录。因此，使用从各种组织分离的RNA通过定量实时RT-PCR确定小鼠和人OSAP的表达谱。结果表明，人和小鼠OSAP表达谱相似; OSAP在类固醇生成组织中显著表达，在肾上腺中观察到最高水平的表达。胎盘作为例外，具有最低水平的OSAP mRNA。免疫组织化学研究表明，小鼠OSAP几乎只定位于卵巢，肾上腺和睾丸的类固醇产生细胞。与几种亚细胞定位算法的预测一致，Y-1小鼠肾上腺皮质细胞的双标记研究表明OSAP存在于线粒体中。由于其在类固醇生成细胞中的丰富表达和线粒体定位，确定了OSAP在类固醇生成中的作用。OSAP沉默特异性小干扰RNA显着抑制8-溴腺苷-cAMP诱导的Y-1细胞孕酮的产生。OSAP水平的降低导致线粒体片段化和线粒体DNA的细胞含量降低，表明线粒体丰度降低。最后，8-溴腺苷-cAMP不调节Y-1细胞中的OSAP蛋白表达，这与已知由cAMP诱导的其它类固醇生成组分的情况相同。总的来说，这些结果表明，OSAP参与类固醇生成，可能是通过其维持线粒体丰度和形态的能力。（内分泌学150：3353-3359，2009）
Ovary-specific acidic protein (OSAP) is a novel molecule discovered from a genomic project designed to identify ovary-selective genes in mice. Whereas public databases suggest extraovarian expression of OSAP, its tissue distribution has not yet been well documented. Thus, the expression profile of mouse and human OSAP was determined by quantitative real-time RT-PCR using RNAs isolated from various tissues. The results demonstrate that the human and mouse OSAP expression profiles are similar; OSAP is prominently expressed in steroidogenic tissues with the highest level of expression observed in the adrenal gland. Placenta served as an exception and possessed minimal level of OSAP mRNA. Immunohistochemical studies show that mouse OSAP localizes almost exclusively to the steroid-producing cells of the ovary, adrenal gland, and testis. Consistent with predictions made by several subcellular localization algorithms, dual labeling studies in Y-1 mouse adrenocortical cells indicate OSAP resides in the mitochondria. Because of its abundant expression in steroidogenic cells and mitochondrial localization, a role for OSAP in steroidogenesis was determined. OSAP silencing by specific small interfering RNAs significantly inhibits 8-bromoadenosine-cAMP-induced progesterone production in Y-1 cells. Reduction in OSAP levels results in mitochondrial fragmentation and a decrease in the cellular content of mitochondrial DNA, indicative of decreased mitochondrial abundance. Lastly, 8-bromoadenosine-cAMP does not regulate OSAP protein expression in Y-1 cells as is the case for other steroidogenic components known to be induced by cAMP. Collectively these results suggest that OSAP is involved in steroidogenesis, potentially through its ability to maintain mitochondrial abundance and morphology. (Endocrinology 150: 3353-3359, 2009)