Decreased expression of calcium-sensing receptor messenger ribonucleic acids in parathyroid adenomas

Background. The set point for parathyroid hormone (PTH) secretion is increa sed in patients with primary hyperparathyroidism, possibly because of recep tor defect(s). A decreased expression of calcium receptor (CaR) messenger r ibonucleic acid (mRNA) and protein and a decreased expression of the putati ve calcium-sensing CAS (gp330/megalin) protein have been demonstrated in pa rathyroid adenomas. Methods. Expression of CAS mRNA was studied in matched pairs of adenomas an d adenoma-associated biopsy specimens from normal parathyroid glands from 1 5 patients with sporadic primary hyperparathyroidism. Cryostat sections wer e 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 t o 25% (median; range 9% to 80 %) of that of the corresponding biopsy specim ens of normal parathyroid glands. Mo 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 betw een the levels of CAS and CaR mRNA. Conclusions Lowered levels of receptors sensing extracellular calcium (CaR and CAS) probably con tribute to the increased set point for PTH secretion in primary hyperparathyroidism.