TY - JOUR
T1 - The synthetic human parathyroid hormone‐related protein is inhibited by a parathyroid hormone antagonist in rats in vivo
AU - Horiuchi, Noboru
AU - Hongo, Takashi
AU - Clemens, Thomas L.
PY - 1990/6
Y1 - 1990/6
N2 - The structure of a novel protein, parathyroid hormone‐related protein (PTHrP), secreted by human tumors associated with hypercalcemia has recently been determined. Administration of a synthetic fragment of this protein in vivo reproduces features of the clinical paraneoplastic syndrome of humoral hypercalcemia of malignancy and produces biologic responses closely similar to those obtained with parathyroid hormone (PTH). A PTH antagonist designed to reversibly occupy PTH receptors inhibited major actions of the tumor peptide in vivo, including phosphaturia, urinary cAMP excretion, and increased serum ionized calcium. These studies indicate that PTHrP and PTH mediate their bioactivities through shared receptors in vivo and establish a potential specific mechanism‐based approach utilizing PTH antagonists for the therapy of tumor‐associated hypercalcemia.
AB - The structure of a novel protein, parathyroid hormone‐related protein (PTHrP), secreted by human tumors associated with hypercalcemia has recently been determined. Administration of a synthetic fragment of this protein in vivo reproduces features of the clinical paraneoplastic syndrome of humoral hypercalcemia of malignancy and produces biologic responses closely similar to those obtained with parathyroid hormone (PTH). A PTH antagonist designed to reversibly occupy PTH receptors inhibited major actions of the tumor peptide in vivo, including phosphaturia, urinary cAMP excretion, and increased serum ionized calcium. These studies indicate that PTHrP and PTH mediate their bioactivities through shared receptors in vivo and establish a potential specific mechanism‐based approach utilizing PTH antagonists for the therapy of tumor‐associated hypercalcemia.
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U2 - 10.1002/jbmr.5650050603
DO - 10.1002/jbmr.5650050603
M3 - Article
C2 - 2166420
AN - SCOPUS:0025313010
SN - 0884-0431
VL - 5
SP - 541
EP - 545
JO - Journal of Bone and Mineral Research
JF - Journal of Bone and Mineral Research
IS - 6
ER -