Henry M. Kronenberg

PARATHYROID HORMONE BIOSYNTHESIS AND ACTION: Molecular Analysis Of the Parathyroid Hormone Gene and Parathyroid Hormone/Parathyroid Hormone-Related Peptide Receptor

Publisher Summary This chapter discusses the molecular analysis of the parathyroid hormone (PTH) gene and parathyroid hormone-related peptide receptor (PTHrP). The human PTH gene is a single-copy gene that extends over 4200 basepairs of DNA on the short arm of chromosome 11. The gene contains three exons, the first of which is noncoding. The second exon contains the initiator ATG and encodes all of the signal or pre-sequence and most of the short pro-peptide. The third exon encodes the remainder of the pro-sequence, the residues corresponding to the mature hormone, as well as the 3′ noncoding region. PTH/PTHrP receptors from marsupial kidney and from kidney and bone of two mammalian species, human and rat, are highly homologous. PTH and PTHrP bind with equal affinity to similar, perhaps identical, receptors in kidney and bone. PTH/PTHrP receptors stimulate adenylate cyclase with the same efficacy when activated by either ligand or are capable of activating at least two effector molecules, adenylate cyclase and phospholipase C. PTH/PTHrP receptors have significant homology only with the calcitonin and the secretin receptor and little or no similarities with other G protein-linked receptors. These three receptor types represent the first members of a novel family of G protein-linked receptors.