Blind E, Raue F, Knappe V, Schroth J, Ziegler R
Department of Internal Medicine I, Endocrinology and Metabolism, University of Heidelberg, Germany.
Exp Clin Endocrinol. 1993;101(3):150-5. doi: 10.1055/s-0029-1211222.
Parathyroid hormone-related protein (PTHrP) plays a major role in the pathogenesis of humoral hypercalcemia of malignancy. It interacts with the PTH receptor and has therefore a nearly identical effect on bone cells as PTH. However, PTHrP is thought to be less potent than PTH in stimulating adenylate cyclase in canine renal membranes, leading to the hypothesis of a differential efficiency in signal transduction by PTHrP with respect to bone vs kidney. In a homologous model with intact osteoblast-like cells (UMR 106) and primary kidney cells, both from the rat, we have tested N-terminal peptide fragments, based on the rat amino acid sequence 1-34, of PTH and PTHrP. Compared with PTHrP(1-34), rat PTH(1-34) had a similar relative potency in bone cells (85%) and in kidney cells (140%) in its ability to stimulate adenylate cyclase. Human PTH(1-34) was 5.6- to 6.5-fold less potent than rat PTH(1-34) in both cell types. In human osteoblast-like cells (SaOS-2), rat and human PTH were essentially equally potent compared to PTHrP(1-34) (identical sequence in rat and human) in stimulating cAMP accumulation. In conclusion, our study revealed the equipotency of rat PTH(1-34) and PTHrP(1-34) in stimulating intracellular cAMP formation in a homologous system of rat bone and kidney cells. There seemed to be no unique signal transduction mechanism of PTHrP to the adenylate cyclase in rat kidney cells compared with bone cells.
甲状旁腺激素相关蛋白（PTHrP）在恶性肿瘤所致的体液性高钙血症的发病机制中起主要作用。它与甲状旁腺激素（PTH）受体相互作用，因此对骨细胞的作用与PTH几乎相同。然而，在刺激犬肾细胞膜中的腺苷酸环化酶方面，PTHrP的效力被认为低于PTH，这导致了关于PTHrP在骨与肾的信号转导中效率差异的假说。在一个由大鼠完整的成骨细胞样细胞（UMR 106）和原代肾细胞组成的同源模型中，我们测试了基于大鼠1 - 34氨基酸序列的PTH和PTHrP的N端肽片段。与PTHrP(1 - 34)相比，大鼠PTH(1 - 34)在刺激腺苷酸环化酶的能力方面，在骨细胞中具有相似的相对效力（85%），在肾细胞中则为（140%）。在两种细胞类型中，人PTH(1 - 34)的效力比大鼠PTH(1 - 34)低5.6至6.5倍。在人成骨细胞样细胞（SaOS - 2）中，与PTHrP(1 - 34)（大鼠和人序列相同）相比，大鼠和人PTH在刺激环磷酸腺苷（cAMP）积累方面基本具有同等效力。总之，我们的研究揭示了在大鼠骨和肾细胞的同源系统中，大鼠PTH(1 - 34)和PTHrP(1 - 34)在刺激细胞内cAMP形成方面具有同等效力。与骨细胞相比，在大鼠肾细胞中似乎不存在PTHrP作用于腺苷酸环化酶的独特信号转导机制。
