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Parathyroid hormone and parathyroid hormone-related protein

Published on December 1, 2007 Reviewed on May 22, 2022   37 min

A selection of talks on Cardiovascular & Metabolic

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0:00
Hello, I'm Bob Nissenson from the University of California and the Veterans Affairs Medical Centre in San Francisco. This lecture will focus on two fascinating proteins, parathyroid hormone and parathyroid hormone related protein, the genes in coding these two molecules are presumed to be derived from a common ancestral gene, but the functions of the proteins have diverged markedly over evolutionary time. Much of the research in my laboratory over the years has been devoted to gaining a better understanding of the physiology and mechanism of action of these molecules.
0:38
PTH and PTHrP share a number of common features. They are both secreted polypeptides and they share a limited degree of amino acid homology in their N-terminal domain. They have a sufficient degree of conformational homology to allow them to bind to and activate a common G-protein-coupled receptor, the PTH1 receptor. PTH and PTHrP produce similar defects in calcium homeostasis, including high blood calcium or hypercalcemia when overproduced in pathological states in vivo.
1:14
However, there are major differences between PTH and PTHrP, they differ with respect to their physiological roles, sites of expression, mode of action and secretory control. The major physiological role of PTH in terrestrial vertebrates is to maintain adequate levels of plasma calcium in the face of a calcium poor terrestrial environment. By contrast, PTHrP has a large number of functions, including the regulation of cartilage maturation during endochondral bone formation, the promotion of the proper morphogenesis of a number of tissues during development and the relaxation of smooth muscles. PTH is normally produced only by the parathyroid glands. PTHrP production is widespread and is adjacent to sites where it acts. PTH functions as a systemic endocrine hormone, by contrast, PTHrP acts locally in a paracrine fashion. The major factor controlling the secretion of PTH is the concentration of calcium in the circulation. PTHrP production is regulated by specific local cues. The full length secreted form of PTH consists of 84 amino acids.
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Parathyroid hormone and parathyroid hormone-related protein

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