Developmental and Tissue-Specific Regulation of Parathyroid Hormone (PTH)/PTH-Related Peptide Receptor Gene Expression

Abstract

Parathyoid hormone (PTH) and PTH-related peptide (PTHrP) signal through a common PTH/PTHrP receptor (PTHR1). PTH is secreted by the parathyroids and functions in an endocrine manner to regulate extracellular fluid calcium concentrations, largely by interacting with receptors expressed in kidney and bone. PTHrP, on the other hand, is widely expressed and acts by autocrine or paracrine signaling to modulate a range of physiological and developmental responses. PTH1R1 signaling is required both in the adult and during development, and ablation of PTHR1 gene expression results in an embryonic lethal phenotype in both mice and humans. Consequently, the PTHR1 is widely expressed, and transcription of its gene is tissue specific and developmentally regulated. This review focuses on our current knowledge of the mechanisms controlling expression of the PTHR1 gene in humans and in rodents, both during development and in the adult. We also compare the conserved and distinct aspects of PTHR1 gene regulation in the two systems and their bearing on signaling by PTH and PTHrP.