Synthetic human parathyroid hormone-like protein stimulates bone resorption and causes hypercalcemia in rats.

A F Stewart; M Mangin; T Wu; D Goumas; K L Insogna; W J Burtis; A E Broadus

doi:10.1172/JCI113358

Department of Endocrinology, West Haven Veterans Administration Medical Center, Connecticut 06516.

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Department of Endocrinology, West Haven Veterans Administration Medical Center, Connecticut 06516.

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Department of Endocrinology, West Haven Veterans Administration Medical Center, Connecticut 06516.

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Department of Endocrinology, West Haven Veterans Administration Medical Center, Connecticut 06516.

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Department of Endocrinology, West Haven Veterans Administration Medical Center, Connecticut 06516.

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Department of Endocrinology, West Haven Veterans Administration Medical Center, Connecticut 06516.

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Department of Endocrinology, West Haven Veterans Administration Medical Center, Connecticut 06516.

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Published in Volume 81, Issue 2 on February 1, 1988
J Clin Invest. 1988;81(2):596–600. https://doi.org/10.1172/JCI113358.
© 1988 The American Society for Clinical Investigation

Published February 1, 1988 - Version history

Parathyroid hormone-like adenylate cyclase-stimulating proteins (hACSPs) have been implicated as one of the calcemic, bone-resorbing agents in patients with humoral hypercalcemia of malignancy. We report the synthesis of an amino-terminal hACSP fragment, Tyr36 hACSP (1-36) amide. The synthetic hACSP is a potent agonist of renal membrane adenylate cyclase (Km, 1.7 X 10(-10)) and of bone cell adenylate cyclase (Km 1 X 10(-9)M). It is a potent bone-resorbing agent in vitro, stimulating 45Ca release from fetal rat long bones at a concentration of 10(-9) M. When infused via osmotic minipumps into rats, it is also a potent calcemic factor in vivo, inducing a rise in serum calcium from (mean +/- SD) 10.6 +/- 0.6 to 19.7 +/- 3.2 mg/dl when infused at 1.4 micrograms/h and from 9.9 +/- 0.7 to 11.4 +/- 1.2 mg/dl when infused at 0.14 micrograms/h. These findings indicate that biologically active hACSP fragments can be synthesized. One such synthetic peptide possesses the in vitro and in vivo bioactivities demonstrated in native, tumor-derived hACSPs. It is also a potent calcemic, bone-resorbing agent.

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