title: Parathyroid hormone 7-84 induces hypocalcemia and inhibits the parathyroid hormone 1-84 secretory response to hypocalcemia in rats with intact parathyroid glands.
abstract: Biologic effects of large C-terminal parathyroid hormone (PTH) fragments, opposite to those of N-terminal PTH, have been demonstrated. C-terminal PTH fragments are co-secreted with N-terminal PTH from the parathyroids. The aim of our study was to examine whether C-terminal PTH 7-84 regulates secretion of PTH 1-84 and affects the expression of genes of relevance for parathyroid function, PTH, calcium-sensing receptor (CaR), PTH type 1 receptor (PTHR1), and PTH-related peptide (PTHrP) genes in rat parathyroid glands. PTH 7-84 induced a significant decrease in plasma Ca2+ in rats with intact parathyroid glands. Despite the reduction of plasma Ca2+, no stimulation of PTH 1-84 secretion took place. Furthermore, the PTH 1-84 secretory response to EGTA-induced acute and severe hypocalcemia was significantly inhibited by PTH 7-84. During recovery from hypocalcemia, plasma Ca2+ levels were significantly lower in the PTH 7-84-treated group, as compared with the vehicle group, and at the same time plasma PTH 1-84 levels were significantly suppressed. The expression of PTH, CaR, PTHR1, and PTHrP genes in the rat parathyroid glands was not affected by PTH 7-84. The peripheral metabolism of PTH 1-84 was not affected by PTH 7-84. PTH 7-84 did not cross-react with the rat bioactive PTH 1-84 assay. In normal rats with intact parathyroid glands, PTH 7-84 inhibited the PTH 1-84 secretory response to hypocalcemia and induced a significant decrease in plasma Ca2+. These effects of PTH 7-84 on PTH 1-84 secretion and on plasma Ca2+ levels were not associated with significant changes in PTH, PTHR1, CaR, and PTHrP gene expressions in the rat parathyroid glands. It is hypothesized that PTH 7-84 regulates PTH secretion via an autocrine/paracrine regulatory mechanism.
authors.affiliation: Nephrological Department P, Rigshospitalet, Herlev Hospital, University of Copenhagen, DK-2730 Herlev, Denmark.
authors.forename: Jinxing
authors.initials: J
authors.lastname: Huan
authors.forename: Klaus
authors.initials: K
authors.lastname: Olgaard
authors.forename: Lars Bo
authors.initials: LB
authors.lastname: Nielsen
authors.forename: Ewa
authors.initials: E
authors.lastname: Lewin
mesh_terms: D000778:Anesthetics, Dissociative / Q000009:adverse effects; D000818:Animals; D002118:Calcium / Q000097:blood; D004533:Egtazic Acid / Q000009:adverse effects; D006801:Humans; D006996:Hypocalcemia / Q000139:chemically induced / Q000378:metabolism*; D007649:Ketamine / Q000009:adverse effects; D010280:Parathyroid Glands / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000778:Anesthetics, Dissociative; D010281:Parathyroid Hormone; D010446:Peptide Fragments; C414937:parathyroid hormone (7-84); D004533:Egtazic Acid; D007649:Ketamine; D002118:Calcium