Parathyroid Hormone Receptor Antibodies

Parathyroid hormone (PTH), parathyroid hormone-related protein (PTHrP), and tuberoinfundibular peptide of thirty-nine residues (TIP39) are endogenous ligands for the parathyroid hormone type 1 and 2 parathyroid hormone receptors. PTH is a classic endocrine hormone essential for mineral homeostasis. It is synthesized as a pre-pro-protein by chief cells of the parathyroid gland. Its secretion is regulated by plasma calcium levels. Mature PTH is an 84 residue polypeptide. Most of the characterized effects of PTH can be brought about by the first 34 N-terminal residues of this polypeptide, and PTH(1-34) that is the most commonly used receptor ligand. A common receptor for PTH and PTHrP is referred to as the PTH/PTHrP or PTH1 receptor. It is a member of Family B GPCRs. Evidence supports coupling to both Gs and Gq G-proteins. PTH1 receptor signaling via Gs or Gq is regulated in a cell- and ligand-specific manner by β-arrestins and the PDZ protein NHERF1. PTH1 receptor expression is particularly high in skeletal tissues and kidney but it has a nearly ubiquitous tissue distribution. The PTH2 receptor was identified in a sequence based screen for novel Family B GPCRs. It has about 50% sequence identity with the PTH1 receptor. It is most abundant in brain and testes, and low levels have been reported in a number of other tissues. The human PTH2 receptor is potently activated by PTH. Failure to detect PTH synthesis in the brain led to the discovery of TIP39. TIP39 is a high affinity, potent agonist at both the human and rat PTH2 receptors. It has low affinity and negligible agonism at PTH1 receptors. An excellent match between the neuroanatomical distributions of TIP39 and the PTH2 receptor supports the identification of TIP39 as the endogenous ligand of the PTH2 receptor. It seems that PTH analogs trigger cAMP production not only from the plasma membrane, but also from endosomal membranes. This new model proposes that internalization of cell surface ligand-PTH1 receptor complexes into early endosomes maintains cAMP production for an extended period of time.