The parathyroid hormone (PTH)/PTH-related peptide receptor mediates actions of both ligands in murine bone.
Endocrinology
; 139(12): 5194-204, 1998 Dec.
Article
en En
| MEDLINE
| ID: mdl-9832460
ABSTRACT
PTH and PTH-related peptide (PTHrP) have been shown to bind to and activate the same PTH/PTHrP receptor. Recent studies have demonstrated, however, the presence of additional receptors specific for each ligand. We used the PTHrP and PTH/PTHrP receptor gene knock-out models to investigate whether this receptor mediates the actions of both ligands in bone. The similar phenotype of the PTHrP (-/-) and PTH/PTHrP receptor (-/-) animals in the growth plate of the tibia suggests that this receptor mediates the actions of PTHrP. Electron microscopic studies have confirmed the accelerated differentiation and disordered organization of chondrocytes, with the accumulation of large amounts of dispersed glycogen granules in the cytoplasm of proliferative and maturing cells of both genotypes. The contrasting growth plate mineralization patterns of the PTHrP (-/-) and PTH/PTHrP receptor (-/-) mice, however, suggest that the actions of PTHrP and the PTH/PTHrP receptor are not identical. Studies using calvariae from PTH/PTHrP receptor (-/-) embryos demonstrate that this receptor solely mediates the ability of PTH and PTHrP to stimulate adenylate cyclase in bone and to stimulate bone resorption. Furthermore, we show that osteoblasts of PTH/PTHrP receptor (-/-) animals, but not PTHrP (-/-) animals, have decreased levels of collagenase 3, osteopontin, and osteocalcin messenger RNAs. The PTH/PTHrP receptor, therefore, mediates distinct physiologic actions of both PTH and PTHrP.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Hormona Paratiroidea
/
Huesos
/
Proteínas
/
Receptores de Hormona Paratiroidea
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Endocrinology
Año:
1998
Tipo del documento:
Article
País de afiliación:
Estados Unidos