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The synthetic human parathyroid hormone‐related protein is inhibited by a parathyroid hormone antagonist in rats in vivo
Author(s) -
Horiuchi Noboru,
Hongo Takashi,
Clemens Thomas L.
Publication year - 1990
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650050603
Subject(s) - parathyroid hormone , in vivo , medicine , endocrinology , parathyroid hormone related protein , antagonist , parathyroid hormone receptor , receptor , chemistry , calcium metabolism , hormone , calcium , calcium sensing receptor , biology , hormone receptor , cancer , breast cancer , microbiology and biotechnology
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.