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Destabilization of parathyroid hormone mRNA by extracellular Ca2+ and the calcimimetic R-568 in parathyroid cells: role of cytosolic Ca and requirement for gene transcription
Destabilization of parathyroid hormone mRNA by extracellular Ca2+ and the calcimimetic R-568 in parathyroid cells: role of cytosolic Ca and requirement for gene transcription
- Source :
- Journal of Molecular Endocrinology. 40:13-21
- Publication Year :
- 2007
- Publisher :
- Bioscientifica, 2007.
-
Abstract
- Extracellular Ca reduces parathyroid hormone (PTH) levels through several mechanisms, but many details of the intracellular steps involved have been difficult to elucidate because of the lack of a suitable parathyroid cell model. The present studies utilized our Ca-responsive bovine parathyroid organoid culture system (pseudoglands) to examine PTH mRNA in intact parathyroid cells. Increasing medium calcium from 0.4 to 3.0 mM reduced PTH mRNA to 20–30% of basal by 16 h. Reducing medium Ca from 3.0 to 0.4 mM restored PTH mRNA levels over a 24-h period. PTH mRNA was also reduced by the calcimimetic R-568, confirming the role of the calcium-sensing receptor. PTH decay rates were determined by placing pseudoglands in either 0.4 or 3.0 mM Ca for 2 h and then blocking gene transcription. PTH mRNA remained stable for at least 24 h in pseudoglands incubated in 0.4 mM Ca, but fell gradually by 62% in the presence of 3.0 mM Ca. Blocking transcription prior to the addition of high-Ca medium dramatically blunted the Ca-induced degradation of PTH mRNA, indicating that acceleration of PTH mRNA decay by Ca requires gene transcription. Pharmacologic investigation of the signaling pathways involved indicated that the Ca-induced reduction of PTH mRNA did not involve MAP kinase, phospholipase D, or cyclic AMP. However, increasing cytosolic Ca with thapsigargin or the Ca ionophore A23187 decreased PTH mRNA levels. In summary, Ca-mediated destabilization of PTH mRNA requires gene transcription and involves increases in cytosolic Ca.
- Subjects :
- medicine.medical_specialty
Transcription, Genetic
Calcimimetic
RNA Stability
Parathyroid hormone
Biology
Parathyroid Glands
Tissue Culture Techniques
Endocrinology
Internal medicine
Phenethylamines
medicine
Organoid
Extracellular
Animals
RNA, Messenger
Receptor
Molecular Biology
Cells, Cultured
Messenger RNA
Aniline Compounds
Propylamines
Parathyroid chief cell
Parathyroid Hormone
Calcium
Cattle
Signal transduction
hormones, hormone substitutes, and hormone antagonists
Signal Transduction
Subjects
Details
- ISSN :
- 14796813 and 09525041
- Volume :
- 40
- Database :
- OpenAIRE
- Journal :
- Journal of Molecular Endocrinology
- Accession number :
- edsair.doi.dedup.....ade5d1163c4ee035b1b09c54f11a66b7
- Full Text :
- https://doi.org/10.1677/jme-07-0085