Calmodulin and calmodulin-dependent protein kinase II inhibit hormone secretion in human parathyroid adenoma

Lu, Ming; Berglund, Erik; Höög, Anders; Farnebo, Lars‐Ove; Bränström, Robert

doi:10.1677/joe-10-0123

Cited by 17 publications

(14 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Up to one third of the tumour was collected from each sample, while the majority of the tissue was sent to routine histopathological diagnostics. Fresh tissue samples were quickly transferred in cold culturing media to the nearby laboratory, and then isolated and cultured using previously described methods [55]. All experiments were performed within 72 hours after isolation.…”

Section: Methodsmentioning

confidence: 99%

“…Perifusion analyses of PTH secretion were performed essentially as previously described [55]. Cells were first suspended in medium overnight to recover from collagenase digestion and analysed by Trypan blue methodology to confirm high cell viability (>98%).…”

Section: Methodsmentioning

confidence: 99%

“…[55] In brief, isolated cells were grown overnight on glass cover slips to enable attachment. The cover slips were placed in a perifusion chamber at 37°C and loaded with 2.5 µM Fura-2 AM (Invitrogen) in extracellular (EC) perifusion solution supplemented with 1.25 mM CaCl 2 .…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Prolactin Receptor in Primary Hyperparathyroidism – Expression, Functionality and Clinical Correlations

Haglund

Vukojević

et al. 2012

PLoS ONE

View full text Add to dashboard Cite

BackgroundPrimary hyperparathyroidism (PHPT) is an endocrine disorder most commonly affecting women, suggesting a role for female hormones and/or their receptors in parathyroid adenomas. We here investigated the prolactin receptor (PRLr) which is associated with tumours of the breast and other organs.Methodology/Principal FindingsPRLr expression was investigated in a panel of 37 patients with sporadic parathyroid tumours and its functionality in cultured parathyroid tumour cells. In comparison with other tissues and breast cancer cells, high levels of prolactin receptor gene (PRLR) transcripts were demonstrated in parathyroid tissues. PRLr products of 60/70 kDa were highly expressed in all parathyroid tumours. In addition varying levels of the 80 kDa PRLr isoform, with known proliferative activity, were demonstrated. In parathyroid tumours, PRLr immunoreactivity was observed in the cytoplasm (in all cases, n = 36), cytoplasmic granulae (n = 16), the plasma membrane (n = 12) or enlarged lysosomes (n = 4). In normal parathyroid rim (n = 28), PRLr was uniformly expressed in the cytoplasm and granulae. In in vitro studies of short-term cultured human parathyroid tumour cells, prolactin stimulation was associated with significant transcriptional changes in JAK/STAT, RIG-I like receptor and type II interferon signalling pathways as documented by gene expression profiling. Moreover, PRLR gene expression in parathyroid tumours was inversely correlated with the patients’ plasma calcium levels.ConclusionsWe demonstrate that the prolactin receptor is highly abundant in human parathyroid tissues and that PRLr isoforms expression and PRLr subcellular localisation are altered in parathyroid tumours. Responsiveness of PRLr to physiological levels of prolactin was observed in the form of increased PTH secretion and altered gene transcription with significant increase of RIG-I like receptor, JAK-STAT and Type II interferon signalling pathways. These data suggest a role of the prolactin receptor in parathyroid adenomas.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Prolactin Receptor in Primary Hyperparathyroidism – Expression, Functionality and Clinical Correlations

Haglund

Vukojević

et al. 2012

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…Given the observational associations between caffeine, BMD, and PTH, we aimed to explore possible effects of caffeine on PTH secretion from the parathyroid cell. For this purpose, we have applied an established system for studies of human parathyroid cell function in short-term cultures of cells ( 19 – 22 ) from patients with hyperparathyroidism. The effects of caffeine on PTH secretion and PTH gene expression, intracellular Ca 2+ ([Ca 2+ ] i ), cAMP, and PKA activity were assessed as well as expression of ADORA 1 and ADORA 2A .…”

mentioning

confidence: 99%

Inhibition of Parathyroid Hormone Secretion by Caffeine in Human Parathyroid Cells

Farnebo

Bränström

2013

The Journal of Clinical Endocrinology & Metabolism

View full text Add to dashboard Cite

Context and Objective:Caffeine is a highly consumed psychoactive substance present in our daily drinks. Independent studies have reported associations between caffeine consumption, low bone mineral density, and urinary calcium loss, as well as impaired bone development in vitro and in vivo. Calcium (Ca2+), vitamin D, and PTH are critical regulators of bone remodeling. A possible association between caffeine and parathyroid gland function has been suggested in the literature.Design, Setting, and Patients:Effects of caffeine on PTH secretion and Ca2+ levels were determined by batch incubation and Fura-2, respectively, in pathological parathyroid cells. Protein expressions were studied by Western blot and immunohistochemistry in normal and parathyroid adenoma tissues. Alterations in gene expressions of adenosine receptor A1 (ADORA1) and A2 (ADORA2A) and PTH were quantified by PCR; intracellular cAMP levels and protein kinase A activity were analyzed by an antibody-based assay.Results:We studied physiological concentrations of caffeine ranging from 1 to 50 μm and found that 50 μm caffeine caused a significant decrease of PTH secretion and PTH gene expression. This decrease occurred in parallel with a decrease of the intracellular cAMP level, protein kinase A activity, and ADORA1 gene expression, indicating a possible causal relationship. The intracellular level of Ca2+ was unaffected even by high concentrations of caffeine. Protein expressions demonstrated two main targets for caffeine—ADORA1 and ADORA2A.Conclusion:A physiological high dose of caffeine inhibits PTH secretion in human parathyroid cells, possibly due to a decrease of the intracellular level of cAMP. The observation demonstrates a functional link between caffeine and parathyroid cell function.

show abstract

“…Calmodulin and calmodulin-dependent protein kinase II (CaMKII) plays important rules in neuroendocrine cell. In Lu et al [111], CaMKII negatively contributes to the regulation of parathyroid hormone (PTH) secretion via a pathway. Finally, HEC6 has medical implication in metastatic neuroendocrine prostate cancer, breast cancer and metastatic colon carcinoma.…”

Section: Resultsmentioning

confidence: 99%

Computational approaches for disease gene identification

Yang¹

View full text Add to dashboard Cite

show abstract

Calmodulin and calmodulin-dependent protein kinase II inhibit hormone secretion in human parathyroid adenoma

Cited by 17 publications

References 26 publications

Prolactin Receptor in Primary Hyperparathyroidism – Expression, Functionality and Clinical Correlations

Prolactin Receptor in Primary Hyperparathyroidism – Expression, Functionality and Clinical Correlations

Inhibition of Parathyroid Hormone Secretion by Caffeine in Human Parathyroid Cells

Computational approaches for disease gene identification

Contact Info

Product

Resources

About