Structural pharmacology of PTH and PTHrP

Abstract

Parathyroid hormone (PTH) and PTH-related peptide (PTHrP) regulate extracellular phosphate and calcium homeostasis as well as bone remodeling. PTH is a classic endocrine peptide hormone whose synthesis and negative feedback by multiple factors control release from the parathyroid glands. PTHrP is ubiquitously expressed (pre- and postnatally) and acts in an autocrine/paracrine manner. This review considers the structural pharmacology and actions of PTH and PTHrP, biological consequences of inherited mutations, engineered analogs that illuminate similarities and differences in physiologic actions, and targeted therapeutic opportunities.

Keywords: Bone biology; Mineral metabolism; Parathyroid hormone; Parathyroid hormone-related peptide; Receptor signaling.