title: Parathyroid hormone induces bone formation in phosphorylation-deficient PTHR1 knockin mice.
abstract: Activation of G protein-coupled receptors by agonists leads to receptor phosphorylation, internalization of ligand receptor complexes, and desensitization of hormonal response. The role of parathyroid hormone (PTH) receptor 1, PTHR1, is well characterized and known to regulate cellular responsiveness in vitro. However, the role of PTHR1 phosphorylation in bone formation is yet to be investigated. We have previously demonstrated that impaired internalization and sustained cAMP stimulation of phosphorylation-deficient (PD) PTHR1 leads to exaggerated cAMP response to subcutaneous PTH infusion in a PD knockin mouse model. To understand the physiological role of receptor internalization on PTH bone anabolic action, we examined bone parameters of wild-type (WT) and PD knockin female and male mice following PTH treatment. We found a decrease in total and diaphyseal bone mineral density in female but not in male PD mice compared with WT controls at 3-6 mo of age. This effect was attenuated at older age groups. PTH administration displayed increased bone volume and trabecular thickness in the vertebrae and distal femora of both WT and PD animals. These results suggest that PTHR1 phosphorylation does not play a major role in the anabolic action of PTH.
authors.affiliation: Wayne State Univ. School of Medicine, Dept. Internal Medicine/Endocrinology, 1107 Elliman Bldg., 421 E. Canfield Ave., Detroit, MI 48201, USA. ndatta@med.wayne.edu
authors.forename: Nabanita S
authors.initials: NS
authors.lastname: Datta
authors.forename: Tareq A
authors.initials: TA
authors.lastname: Samra
authors.forename: Abdul B
authors.initials: AB
authors.lastname: Abou-Samra
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D015519:Bone Density / Q000187:drug effects / Q000502:physiology; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology; D055879:Gene Knock-In Techniques; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D010006:Osteoblasts / Q000166:cytology; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*; D010281:Parathyroid Hormone / Q000378:metabolism* / Q000494:pharmacology; D010766:Phosphorylation / Q000502:physiology; D061251:Primary Cell Culture; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000235:genetics* / Q000378:metabolism*; D012886:Skull / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D055114:X-Ray Microtomography
chemical_list: D010281:Parathyroid Hormone; D044168:Receptor, Parathyroid Hormone, Type 1