Parathyroid hormone-related protein PTHrP

Iwamura M, Heilman J, Cockett AT, Lilja H, Gershagen S. Alteration of the hormonal bioactivity of parathyroid hormone-related protein (PTHrP) as a result of limited proteolysis by prostate-specific antigen. Urology 1996 48 317-325. 

Parathyroid hormone-related protein (PTHrP)] (protein)... 

Parathyroid Hormone-Related Protein PTHrP was discovered in 1987 by investigators studying the mechanism by which certain cancers produce humoral hypercalcemia of malignancy (HHM). ... 

Parathyroid hormone-related protein (PTHrP) Predominant factor responsible for hypercalcemia of malignancy. PTHrP functions through the activation of PTH receptor it has paracrine functions, it regulates rate of cartilage differentiation and increase placental calcium transport, it may also have PTHrP specific receptors. 

A second member of the parathyroid hormone family, parathyroid hormone-related protein (PTHrP), is quite similar to PTH in amino acid sequence and protein structure. Like PTH, it activates the parathyroid hormone receptor causing increased bone resorption and renal tubular calcium reabsorption. Increased serum concentrations of parathyroid hormone-related protein are the predominant cause of hypercalcemia in cancer patients with solid tumors. This observation led to its discovery and to the elucidation of its many cellular functions in normal tissues. In contrast to PTH, which is expressed only in parathyroid glands, PTHrP is detected in many tissues in fetuses and adults it is found in epithelia, mesenchymal tissues, endocrine glands, and the central nervous system. This protein is also the principal regulator of placental calcium transport to the fetus. 

Some cancers may cause hyper-calcaemia. In many cases this is due to the secretion of parathyroid hormone related protein, PTHrP, so-called because of its relationship with PT H both in its structure and function. 

FIGURE 96-4. Pathophysiology of the hypercalcemia of malignancy. PTHrP, parathyroid hormone-related protein TGF-P, transforming growth factor P TNF-a, tumor necrosis factor alpha Ca2+, calcium IL-1, interleukin 1 IL-2, interleukin 2. 

Figure 49-22 PTHrP in normal subjects and patients with malignancies and other disorders. Hatched area indicates the normal reference interval. (Adapted from Pandian AIR, Morgan CH, Carlton E, Segre GV. Modified /mmunorod/ometr/c ossoy of parathyroid hormone-related protein clinical app/icatfon in the differential diagnosis of hypercalcemia. Clin Chem 1992 38 282 SS.)...

A diagnostic decision chart is shown in Figure 1. Primary hyperparathyrouHsm is most often due to a single parathyroid adenoma which secretes PTH independently of feedback control by plasma calcium. Hypercalcaemia associated with malignancy is the commonest cause of a high calcium in a hospital population. Some tumours secrete a protein called PTHrP (parathyroid hormone-related protein) which has PTH-like properties. 

Sox4 a member of the SOX (SRY-related HMG-box) family of transcription factors involved in the regulation of embryonic development and in the determination of the cell fate. The encoded protein may act as a transcriptional regulator after forming a protein complex with other proteins, such as syndecan binding protein (syntenin). The protein may also function in the apoptosis pathway leading to cell death as well as to tumorigenesis and may mediate downstream effects of parathyroid hormone (PTH) and PTH-related protein (PTHrP) in bone development. 

Turner, P.R. et al. (2000) Apoptosis mediated by activation of the G protein-coupled receptor for parathyroid hormone (PTH)/PTH-related protein (PTHrP). Molecular Endocrinology, 14, 241-254. 

HIV human immune deficiency virus HPV human papillomavirus HSV herpes simplex virus ICAM intercellular adhesion molecule IL interleukin IL-la interleukin 1 a LNA locked nucleic acid mRNA messenger RNA NK natural killer PKC protein kinase C ply rC poly ribocytosine PNA peptide nucleic acid poly rl poly ribinosine PTHrP parathyroid hormone-related peptide thermal melting temperature change in relative to DNA TAR transactivator response element VSV vesicular stomatitis virus... 

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