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Decreased expression of calcium-sensing receptor messenger ribonucleic acids in parathyroid adenomas
F Farnebo1, A Höög, K Sandelin
1Department of Molecular Medicine, Karolinska Hospital, Stockholm, Sweden.
Background:
The set point for parathyroid hormone (PTH) secretion is increased in patients with primary hyperparathyroidism, possibly because of receptor defect(s). A decreased expression of calcium receptor (CaR) messenger ribonucleic acid (mRNA) and protein and a decreased expression of the putative calcium-sensing CAS (gp330/megalin) protein have been demonstrated in parathyroid adenomas.
Methods:
Expression of CAS mRNA was studied in matched pairs of adenomas and adenoma-associated biopsy specimens from normal parathyroid glands from 15 patients with sporadic primary hyperparathyroidism. Cryostat sections were hybridized with an oligonucleotide complementary to CAS mRNA, rinsed, air dried, and exposed to x-ray film for semiquantification of radioactivity.
Results:
Expression of CAS mRNA in the adenomas was lowered significantly to 25% (median; range 9% to 80%) of that of the corresponding biopsy specimens of normal parathyroid glands. No correlation was seen between CAS mRNA in the adenoma and preoperative serum calcium levels, PTH level, or weight of the adenoma. The levels of CAS mRNA were significantly lower than those observed previously for CaR mRNA. There was no significant correlation between the levels of CAS and CaR mRNA.
Conclusions:
Lowered levels of receptors sensing extracellular calcium (CaR and CAS) probably contribute to the increased set point for PTH secretion in primary hyperparathyroidism.
Insights
Primary hyperparathyroidism involves increased parathyroid hormone (PTH) secretion due to potential receptor defects. This study found significantly lower calcium-sensing (CAS) messenger RNA (mRNA) levels in parathyroid adenomas, suggesting a role in the condition.
Area of Science:
- Endocrinology
- Molecular Biology
Background:
- Primary hyperparathyroidism is characterized by an elevated set point for parathyroid hormone (PTH) secretion.
- This elevation may stem from defects in calcium-sensing receptors.
- Reduced expression of calcium receptor (CaR) and calcium-sensing (CAS) proteins and mRNA has been observed in parathyroid adenomas.
Purpose of the Study:
- To investigate the expression levels of calcium-sensing (CAS) messenger ribonucleic acid (mRNA) in parathyroid adenomas from patients with sporadic primary hyperparathyroidism.
- To compare CAS mRNA expression in adenomas with matched normal parathyroid tissue.
Main Methods:
- Studied CAS mRNA expression in matched pairs of parathyroid adenomas and normal parathyroid biopsy specimens from 15 patients.
- Utilized in situ hybridization with an oligonucleotide probe complementary to CAS mRNA.
- Quantified radioactivity on X-ray film for semiquantification of CAS mRNA expression.
Main Results:
- CAS mRNA expression was significantly reduced in parathyroid adenomas, averaging 25% of levels in corresponding normal parathyroid tissue.
- No correlation was found between CAS mRNA levels and preoperative serum calcium, PTH levels, or adenoma weight.
- CAS mRNA levels were significantly lower than previously reported CaR mRNA levels, with no significant correlation between CAS and CaR mRNA.
Conclusions:
- Reduced expression of extracellular calcium-sensing receptors, including CaR and CAS, likely contributes to the elevated PTH secretion set point in primary hyperparathyroidism.
- These findings highlight the potential role of impaired calcium sensing in the pathophysiology of primary hyperparathyroidism.