Parathyroid hormone-related protein

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. [Pg.887]

PTHrP is released during lactation and its levels increase about 10,000-fold over the levels found in the serum of nonlactating women. Receptors for PTHrP are present in the intestinal epithelium and the hormone may play a physiologic role in the development of the alimentary tract. However, infants raised on soy milk formulas that do not contain the hormone are healthy thus, the hormone is not essential. [Pg.887]

The principal target organ for calcitonin is bone, but renal excretion of calcium and phosphate is also directly affected. In bone and kidney, calcitonin activates adenylate cyclase by binding to a distinct class of G-protein-coupled receptors. Calcitonin may also exert effects on cytosolic Ca + and IP3 levels by activation of the phospholipase [Pg.887]

Amino acid sequence of human calcitonin. [Reproduced with permission from R. K. Murray, D. K. Granner, R A. Mayes, and V. W. Rodwell, Norwalk Harper s Biochemistry, 21st ed. Appleton Lange, Norwalk, 1988. 1988 Appleton Lange. ] [Pg.887]

C signal transduction pathway. Secretion of calcitonin is stimulated by hypercalcemia but the effect of the hormone on calcium transport appears to be secondary to increased phosphate uptake by target cells. The number and activity of osteoclasts are decreased, and urinary excretion of hy-droxyproline is decreased, Calcitonin may also inhibit release of calcium from the extracellular fluid calcium pool, but it increases calcium and phosphate excretion by renal tubules. Some tubular cells respond to calcitonin, PTH, and vasopressin, while others respond only to one or two of these hormones. In general, the actions of calcitonin in kidney and in bone are antagonistic to those of PTH. Calcitonin decreases secretion of gastrin and of gastric acid, and inhibits bile flow. [Pg.888]

The delicate balance maintained by these factors is altered in patients with cancer by two principal mechanisms tumor production of humoral factors that alter calcium metabolism (humoral hypercalcemia) and local osteolytic activity from bone metastases.27 Humoral hypercalcemia causes around 80% of all hypercalcemia cases and is mediated primarily by systemic secretion of parathyroid hormone-related protein... [Pg.1482]

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. [Pg.1483]

Escande, B., Lindner, V., Massfelder, T., Helwig, J. J., and Simeoni, U. (2001). Developmental aspects of parathyroid hormone-related protein biology. Semin. Perinatol. 25, 76-84. [Pg.72]

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. [Pg.73]

P2. Pandian, M. R., Morgan, C. H., Carlton, E., and Serge, G. V., Modified immunoradiometric assay of parathyroid hormone-related protein Clinical application in the differential diagnosis of hypercalcemia. Clin. Chem. 38, 282-288 (1992). [Pg.292]

Parathyroid hormone-related protein receptor is a GPCR that acts via a Gas (and elevation of cAMP) or via Gaq (to activate PLC, increase IP3 and thence increase cytosolic Ca2+). PTH increases bone resorption and reabsorption of Ca2+ in the kidney with consequent elevation of blood Ca2+. Calcitonin, which binds to a GPCR that acts via a Gas to elevate C.AMP, has opposing effects to those of PTH. [Pg.167]

Parathyroid hormone/ parathyroid hormone-related protein receptor (PTH-R)... [Pg.225]

Parathyroid hormone-related protein (PTHrP)] (protein)... [Pg.225]

E. Peggion, A. Bisello, M. Rosenblatt, M. Chorev, D. F. Mierke, Mono- and bicyclic analogs of parathyroid hormone-related protein. 2. Conformational analysis of antagonists by CD, NMR, and distance geometry calculations, Biochemistry 1997, 36, 3300-3307. [Pg.323]

Parathyroid Hormone-Related Protein PTHrP was discovered in 1987 by investigators studying the mechanism by which certain cancers produce humoral hypercalcemia of malignancy (HHM). ... [Pg.1928]

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.)...

Burtis W). Parathyroid hormone-related protein structure, function, and measurement. Clin Chem 1992 38 2171-83. [Pg.1947]

Burtis WJ, Brady TG, Orlofif JJ, Ersbale JB, WarreU RP Jr, Olson BR, et al. Immunochemical characterization of circulating parathyroid hormone-related protein in patients with humoral hypercalcemia of cancer. [Pg.1947]

Fraser WD, Robinson J, Lawton R, Durham B, Gallacher SJ, Boyle IT, et al. Clinical and laboratory studies of a new immunoradiometric assay of parathyroid hormone-related protein. Clin Chem 1993 39 414-19. [Pg.1950]

Hutchesson ACJ, Hughes SV, Bowden SJ, Ratdiffe WA. In vitro stability of endogenous parathyroid hormone-related-protein in blood and plasma. Ann Clin Biochem 1994 31 35-9. [Pg.1953]

Levin GE, Nisbet JA, Stability of parathyroid hormone-related protein and parathyroid hormone at room temperature. Ann Clin Biochem 1994 31 497-500. [Pg.1955]

Moseley JM, Gillespie MT. Parathyroid hormone-related protein. Grit Rev Clin Lab Sci 1995 32 299-343. [Pg.1957]

Orloff JJ, Reddy D, De Papp AE, Soifer NE, Stewart AF. Parathyroid hormone-related protein as a prohormone posttranslational processing and receptor interactions. Endocr Rev 1994 15 40-60. [Pg.1958]

Papantoniou NE, Papapetrou PD, AntsakUs AJ, Kon-toleon PE, Mesogitis SA, Aravantinos D. Circulating levels of immunoreactive parathyroid hormone-related protein and intact parathyroid hormone in human fetuses and newborns. Eur J Endocrinol 1996 134 437-42. [Pg.1958]

Plulbrick WM, Wysolmersld JJ, Galbraith S, Holt E, Holt E, Orloff JJ, et al. Defining the roles of parathyroid hormone-related protein in normal physiology. Physiol Rev 1996 76 127-73. [Pg.1958]

Ralston SH> Danks J, Hayman J, Fraser WD, Stewart CS, Martin TJ. Parathyroid hormone-related protein of malignancy immunohistochemical and biochemical studies in normal and hypercalcemic patients with cancer. J Clin Pathol 1991 44 472-6. [Pg.1959]

Stewart AF, Broadus AE. Clinical review 16 parathyroid hormone-related proteins coming of age in the 1990s. J Endocrinol Metab 1990 71 1410-4. [Pg.1962]

Strewler GJ. The parathyroid hormone-related protein. Endocrinol Metab Cfin North Am 2000 29 629-45. [Pg.1962]

Tsuchihashi T, Yamaguchi K, Miyake Y, Otsubo K, Nagasaki K, Honda S, et al. Parathyroid hormone-related protein in tumor tissues obtained from patients with humoral hypercalcemia of malignancy. JNCI 1990 82 40-4. [Pg.1964]

Wysolmerski JJ, Broadus AE. Hypercalcemia of malignancy the central role of parathyroid hormone-related protein. Annu Rev Med 1994 45 189-200. [Pg.1965]

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