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A Parathyroid Hormone Inhibitor in Vivo: Design and Biological Evaluation of a Hormone Analog

1983; American Association for the Advancement of Science; Volume: 220; Issue: 4601 Linguagem: Inglês

10.1126/science.6302844

1095-9203

Noboru Horiuchi, Michael F. Holick, John T. Potts, Michael Rosenblatt,

Fibroblast Growth Factor Research

A synthetic analog of bovine parathyroid hormone (bPTH), [tyrosine-34]bPTH-(7-34)NH 2 , was found to inhibit parathyroid hormone action in vivo. When the analog and parathyroid hormone were infused simultaneously to rats at a molar ratio of 200 to 1, the analog inhibited the excretion of urinary phosphate and adenosine 3′,5′-monophosphate. When infused alone at the same dose rate, the analog was devoid of agonist activity. The compound was prepared by following design principles developed for inhibitors of parathyroid hormone, and is believed to be the first antagonist of parathyroid hormone that is effective in vivo.