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Acute Parathyroid Hormone Injection Increases C-Terminal but Not Intact Fibroblast Growth Factor 23 Levels
- Source :
- Endocrinology. 158:1130-1139
- Publication Year :
- 2017
- Publisher :
- The Endocrine Society, 2017.
-
Abstract
- The acute effects of parathyroid hormone (PTH) on fibroblast growth factor 23 (FGF23) in vivo are not well understood. After a single subcutaneous PTH (1–34) injection (50 nmol/kg) in mice, FGF23 levels were assessed in plasma using assays that measure either intact alone (iFGF23) or intact/C-terminal FGF23 (cFGF23). Furthermore, FGF23 messenger RNA (mRNA) and protein levels were assessed in bone. In addition, we examined the effects of PTH treatment on FGF23 production in vitro using differentiated calvarial osteocyte-like cells. cFGF23 levels increased by three- to fivefold within 2 hours following PTH injection, which returned to baseline by 4 hours. In contrast, iFGF23 levels remained unchanged for the first 2 hours, yet declined to ∼60% by 6 hours and remained suppressed before returning to baseline after 24 hours. Using homozygous mice for an autosomal dominant hypophosphatemic rickets–FGF23 mutation or animals treated with a furin inhibitor, we showed that cFGF23 and iFGF23 levels increased equivalently after PTH injection. These findings are consistent with increased FGF23 production in bone, yet rapid cleavage of the secreted intact protein. Using primary osteocyte-like cell cultures, we showed that PTH increased FGF23 mRNA expression through cyclic adenosine monophosphate/protein kinase A, but not inositol triphosphate/protein kinase C signaling; PTH also increased furin protein levels. In conclusion, PTH injection rapidly increases FGF23 production in bone in vivo and in vitro. However, iFGF23 is rapidly degraded. At later time points through an unidentified mechanism, a sustained decrease in FGF23 production occurs.
- Subjects :
- Male
0301 basic medicine
Fibroblast growth factor 23
medicine.medical_specialty
Parathyroid hormone
030209 endocrinology & metabolism
Fibroblast growth factor
Osteocytes
Bone and Bones
Injections
Protein kinase C signaling
Mice
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Endocrinology
Protein Domains
In vivo
Internal medicine
medicine
Animals
Cyclic adenosine monophosphate
Protein kinase A
Furin
Cells, Cultured
Mice, Knockout
biology
Peptide Fragments
Fibroblast Growth Factors
Mice, Inbred C57BL
Fibroblast Growth Factor-23
stomatognathic diseases
030104 developmental biology
chemistry
Parathyroid Hormone
biology.protein
Female
Special Section: Metabolism in Endocrine Health and Disease
Subjects
Details
- ISSN :
- 19457170 and 00137227
- Volume :
- 158
- Database :
- OpenAIRE
- Journal :
- Endocrinology
- Accession number :
- edsair.doi.dedup.....c93c55f4db623dfc51a0f2f7c0b36f99