Matsushita H, Usui M, Hara M, Shishiba Y, Nakazawa H, Honda K, Torigoe K, Kohno K, Kurimoto M
Department of Pathology, Toranomon Hospital, Tokyo, Japan.
Am J Pathol. 1997 Mar;150(3):861-71.
Parathyroid-hormone-related protein (PTHrP) is widely expressed not only in malignant tumors but also in both epithelial and nonepithelial cells of normal tissues. Secreted PTHrP is suspected to act as a paracrine or autocrine regulator. However, little is known about its secretory pathway. To cast light on this question, we studied the intracytoplasmic distribution of parathyroid hormone (PTH) and PTHrP immunohistochemically and immunoelectron microscopically in 10 surgically resected parathyroid adenomas. Double immunostaining was performed using anti-PTH antibody and a newly established anti-PTHrP antibody to reveal the relationship between their two distributions. Additional examination by cell immunoblot assay was performed to determine whether both PTH and PTHrP are secreted simultaneously. Both PTH and PTHrP were actually secreted from individual parathyroid cells simultaneously on cell immunoblot assay. Immunohistochemically, there were two different types of adenoma cells, i.e., one positive only for PTH and the other positive for both PTH and PTHrP. PTH was distributed linearly or fine granularly along the cytoplasmic membrane, whereas PTHrP was distributed diffusely or coarse granularly in the cytoplasm. The intracytoplasmic distributions of PTH and PTHrP often overlapped. Immunoelectron microscopical examination demonstrated that PTHrP co-localized with PTH in the same secretory granules. The results clearly demonstrated that PTHrP can be co-secreted with PTH via a regulated pathway using secretory granules.
甲状旁腺激素相关蛋白（PTHrP）不仅在恶性肿瘤中广泛表达，在正常组织的上皮细胞和非上皮细胞中也均有表达。分泌型PTHrP被怀疑作为旁分泌或自分泌调节因子发挥作用。然而，其分泌途径却鲜为人知。为阐明这一问题，我们采用免疫组织化学和免疫电子显微镜技术，对10例手术切除的甲状旁腺腺瘤中甲状旁腺激素（PTH）和PTHrP的胞内分布进行了研究。使用抗PTH抗体和新制备的抗PTHrP抗体进行双重免疫染色，以揭示二者分布之间的关系。通过细胞免疫印迹分析进行进一步检测，以确定PTH和PTHrP是否同时分泌。在细胞免疫印迹分析中，PTH和PTHrP实际上均从单个甲状旁腺细胞中同时分泌。免疫组织化学结果显示，存在两种不同类型的腺瘤细胞，即一种仅对PTH呈阳性，另一种对PTH和PTHrP均呈阳性。PTH沿细胞膜呈线性或细颗粒状分布，而PTHrP在细胞质中呈弥漫性或粗颗粒状分布。PTH和PTHrP的胞内分布常相互重叠。免疫电子显微镜检查表明，PTHrP与PTH共定位于同一分泌颗粒中。结果清楚地表明，PTHrP可通过利用分泌颗粒的调节途径与PTH共同分泌。
