Receptors for parathyroid hormone-related protein (PTHrP)

甲状旁腺相关蛋白（PTHrP）广泛分布于人体正常组织中。PTHrP在正常组织中的生理功能被怀疑是旁分泌效应器。为了揭示PTHrP在胞浆内的分布，我们首先建立了抗PTHrP的单克隆抗体（克隆号：MMUN-034）。甲状旁腺中有少量PTHrP阳性细胞，而增生的甲状旁腺中常可见PTHrP阳性细胞结节状生长。在已建立的大鼠甲状旁腺细胞系PTHrP细胞中，PTHrP呈弥漫性分布，呈类似波形蛋白的网状结构。重组PTHrP刺激PTr细胞后，PTH在胞浆内的分布发生明显变化。即，PTHrP刺激1小时后，位于核周围的PTr细胞中的甲状旁腺激素重新分布到细胞膜上。细胞外钙离子可抑制甲状旁腺细胞释放PTHrP。PTHrP在甲状旁腺细胞生长和PTH分泌中起重要作用，在T淋巴细胞和B淋巴细胞中均有表达。PTHrP定位于活化T淋巴细胞与B淋巴细胞接触的胞浆口。因此，PTHrP可能通过调节T、B淋巴细胞间的接触，在T、B淋巴细胞间的共刺激系统中发挥重要作用。

Parathyroid hormone-related protein (PTHrP) is known to widely distribute in the normal human tissues. The physiological functions of PTHrP in normal tissues are suspected to be a paracrine effector. To reveal intracytoplasmic distribution of PTHrP,we firsts established a monoclonal antibody against PTHrP (clone No. : MMUN-034). There are a few parathyroid cells positive for PTHrP,whereas nodular growth of PTHrP positive cell is frequently found in hyperplastic parathyroid glands. In PTr cells, established rat parathyroid cell line, PTHrP was distributed diffusely with net-work like structure similar to that of vimentin. Intracytoplasmic distribution of PTH significantly changed after the stimulation of recombinant PTHrP in PTr cells. That is, parathyroid hormone in PTr cells localized around the nuclei redistributed to the cell membrane 1 hour after PTHrP stimulation. And PTHrP release from parathyroid cells was inhibited by the extracellular calcium. Therefore, PTHrP in the parathyroid gland is suspected to have an important role in the control of cell growth and PTH secretion.PTHrP was also expressed in both T and B lymphocytes. PTHrP in the activated T lymphocytes was localized in the cytoplasmic snout by which T lymphocytes may contact with B lymphocytes. Thus, PTHrP was suspected to have some important roles in the costimulation system between T and B lymphocytes through the regulation of cell contact.