Secretion of PTH is regulated by extracellular
calcium via
calcium receptors (CaR) on the parathyroid cell surface. Recent studies have shown a decreased expression of CaR
messenger RNA (
mRNA) and CaR
protein in pathological parathyroids. We studied the expression of CaR
mRNA in pairs of
adenoma and
adenoma-associated normal gland from the same patients (n = 17) and in biopsies of normal parathyroid glands of normocalcemic subjects (n = 4) using in situ hybridization with
oligonucleotide probes on frozen sections. No down-regulation of CaR
mRNA caused by
hypercalcemia could be demonstrated in the normal
adenoma-associated parathyroids when compared with the normal parathyroids of normocalcemic subjects. In contrast, CaR
mRNA in the
adenomas was significantly reduced to 64% (median; range 41-98) of the corresponding normal
adenoma-associated glands. No correlation was seen between CaR
mRNA in the
adenoma and preoperative serum
calcium, PTH, or weight of the
adenoma. Loss of heterozygosity studies were performed on
adenomas using markers for the locus of the CaR gene on chromosome 3q. No allelic loss was demonstrated, excluding allelic loss as the cause for decreased CaR
mRNA expression in the
adenomas. It is concluded that the lowered levels of CaR
mRNA in
parathyroid adenomas may contribute to the increased set point of PTH secretion. In large
adenomas the increased cell mass seems to be more important for the increased secretion of PTH.