14 research outputs found
Deletion of the Noncoding GNAS Antisense Transcript Causes Pseudohypoparathyroidism Type Ib and Biparental Defects of GNAS Methylation in cis
Evaluating the Ligand Specificity of Zebrafish Parathyroid Hormone (PTH) Receptors: Comparison of PTH, PTH-Related Protein, and Tuberoinfundibular Peptide of 39 Residues
Studies of the N-Terminal Region of a Parathyroid Hormone-Related Peptide(1–36) Analog: Receptor Subtype-Selective Agonists, Antagonists, and Photochemical Cross-Linking Agents1
Circulating Fibroblast Growth Factor 23 in Patients with End-Stage Renal Disease Treated by Peritoneal Dialysis Is Intact and Biologically Active
Context: Fibroblast growth factor 23 (FGF23) regulates phosphorus homeostasis and vitamin D metabolism. Circulating FGF23 levels are elevated in inherited and acquired hypophosphatemic disorders that can cause rickets or osteomalacia. Particularly increased concentrations of FGF23 are observed in patients with chronic kidney disease (CKD), in which increased FGF23 is associated with more rapid disease progression, improved bone mineralization, the development of left ventricular hypertrophy, and increased mortality
Identification and Characterization of the Murine and Human Gene Encoding the Tuberoinfundibular Peptide of 39 Residues
Defective O-Glycosylation due to a Novel Homozygous S129P Mutation Is Associated with Lack of Fibroblast Growth Factor 23 Secretion and Tumoral Calcinosis
Background: Homozygous mutations in fibroblast growth factor (FGF23) have recently been described as the genetic cause of one form of hyperphosphatemic tumoral calcinosis (HFTC). However, it remained unclear to date how these mutations lead to loss of biologically active FGF23 in the circulation
Backbone Modification Provides a Long-Acting Inverse Agonist of Pathogenic, Constitutively Active PTH1R Variants
Parathyroid hormone 1 receptor (PTH1R) plays a key role
in mediating
calcium homeostasis and bone development, and aberrant PTH1R activity
underlies several human diseases. Peptidic PTH1R antagonists and inverse
agonists have therapeutic potential in treating these diseases, but
their poor pharmacokinetics and pharmacodynamics undermine their in
vivo efficacy. Herein, we report the use of a backbone-modification
strategy to design a peptidic PTH1R inhibitor that displays prolonged
activity as an antagonist of wild-type PTH1R and an inverse agonist
of the constitutively active PTH1R–H223R mutant both in vitro
and in vivo. This peptide may be of interest for the future development
of therapeutic agents that ameliorate PTH1R malfunction
Mechanisms of Ligand Binding to the Parathyroid Hormone (PTH)/PTH-Related Protein Receptor: Selectivity of a Modified PTH(1–15) Radioligand for GαS-Coupled Receptor Conformations
Dominant-Negative GCMB Mutations Cause an Autosomal Dominant Form of Hypoparathyroidism
Context: Hypoparathyroidism (HP) is characterized by low PTH levels, hypocalcemia, and hyperphosphatemia. Heterozygous mutations in pre-pro-PTH or the calcium-sensing receptor (CaSR) cause some forms of autosomal dominant HP (AD-HP). Furthermore, homozygous mutations in glial cells missing B (GCMB) have been implicated in autosomal recessive HP (AR-HP). In most other HP patients, however, the molecular defect remains undefined