Cetin Y, Aunis D, Bader M F, Galindo E, Jörns A, Bargsten G, Grube D
Department of Anatomy, Hannover Medical School, Federal Republic of Germany.
Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2360-4. doi: 10.1073/pnas.90.6.2360.
Chromogranin A (CGA) is a secretory protein present in the adrenal medulla and in a variety of endocrine organs. This protein may serve as precursor for pancreastatin (PST) and for other biologically active peptides. Recently, chromostatin (CST), a CGA derivative, has been identified that possesses high biological activity. The cellular distribution of CST in various endocrine organs is completely unknown. Using immunohistochemistry on plastic sections, we investigated the occurrence and cellular distribution of CST, PST, and CGA in human endocrine pancreas of healthy and diseased states and in the adrenal medulla. In the normal and diabetic pancreas, CST immunoreactivity was localized exclusively in beta cells, which were mostly unreactive for PST and CGA. Both latter peptides were confined mainly to glucagon (alpha) cells. Insulinoma cells displayed strong insulin, PST, and CGA immunoreactivities, but they were faintly immunoreactive for CST or unreactive. Adrenal chromaffin cells exhibited strong immunoreactivity for CGA but lacked CST and PST immunoreactivities. Based on the peculiar distributive pattern of CST, PST, and CGA, we suggest that CGA is differentially processed in chromaffin and islet tissues and in insulinoma cells. The unique cellular localization of CST in the endocrine pancreas of normal and pathological conditions may indicate that CST is involved in beta-cell function.
嗜铬粒蛋白A(CGA)是一种存在于肾上腺髓质和多种内分泌器官中的分泌蛋白。这种蛋白质可能是胰抑制素(PST)和其他生物活性肽的前体。最近,已鉴定出一种具有高生物活性的CGA衍生物嗜铬粒抑制素(CST)。CST在各种内分泌器官中的细胞分布完全未知。我们使用塑料切片免疫组织化学方法,研究了CST、PST和CGA在健康和患病状态的人类内分泌胰腺以及肾上腺髓质中的存在情况和细胞分布。在正常和糖尿病胰腺中,CST免疫反应性仅定位于β细胞,而β细胞对PST和CGA大多无反应。后两种肽主要局限于胰高血糖素(α)细胞。胰岛素瘤细胞显示出强烈的胰岛素、PST和CGA免疫反应性,但它们对CST免疫反应微弱或无反应。肾上腺嗜铬细胞对CGA表现出强烈的免疫反应性,但缺乏CST和PST免疫反应性。基于CST、PST和CGA独特的分布模式,我们认为CGA在嗜铬组织、胰岛组织和胰岛素瘤细胞中存在差异加工。CST在正常和病理状态下的内分泌胰腺中的独特细胞定位可能表明CST参与β细胞功能。