Vasavada R C, Garcia-Ocana A, Massfelder T, Dann P, Stewart A F
Division of Endocrinology, Pittsburgh VA Medical Center, Pennsylvania, USA.
Recent Prog Horm Res. 1998;53:305-38; discussion 338-40.
Parathyroid hormone-related protein was discovered as the causative agent responsible for the common paraneoplastic syndrome, humoral hypercalcemia of malignancy. It is now clear that the PTHrP gene is expressed in virtually every cell and tissue in the body at some point in development or adult life and that the peptide is critical for normal life. Two of the tissues that produce PTHrP are the insulin-producing beta cells of the pancreatic islet and the vascular smooth muscle cells of the arterial wall. In this review, the physiologic roles of PTHrP in the islet and in the arterial wall are explored. PTHrP is a classical neuroendocrine prohormone that undergoes extensive post-translational processing to yield a family of daughter peptides that are the mature secretory forms of the peptide. In addition to its ability to act as a traditional endocrine, paracrine, or autocrine factor, PTHrP appears to be able to act as an "intracrine" factor as well, directly entering the nucleus after translation and stimulating proliferation, apoptosis, and perhaps other cellular responses as well. The cell biology underlying this phenomenon is also explored herein.
甲状旁腺激素相关蛋白被发现是导致常见副肿瘤综合征——恶性肿瘤体液性高钙血症的致病因子。现在已经清楚，PTHrP基因在机体几乎每个细胞和组织的发育或成年期的某个阶段都会表达，并且该肽对正常生命至关重要。产生PTHrP的两个组织是胰岛中产生胰岛素的β细胞和动脉壁的血管平滑肌细胞。在这篇综述中，探讨了PTHrP在胰岛和动脉壁中的生理作用。PTHrP是一种经典的神经内分泌前激素，经过广泛的翻译后加工产生一系列子代肽，这些子代肽是该肽的成熟分泌形式。除了具有作为传统内分泌、旁分泌或自分泌因子的能力外，PTHrP似乎还能够作为“内分泌”因子，在翻译后直接进入细胞核并刺激增殖、凋亡，或许还能引发其他细胞反应。本文还探讨了这一现象背后的细胞生物学机制。
