Heterogeneous expression of receptor mRNAs in parathyroid glands of secondary hyperparathyroidism

Background. Secondary hyperparathyroidism (HPT) is characterized by inappro priate control of parathyroid hormone (PTH) secretion and asymmetric hyperp lasia of the parathyroid glands. Receptors for calcium and vitamin D are in volved in the control of secretion, as well as parathyroid cell proliferati on. Defective receptor mechanisms therefore may play a role in the pathogen ensis of secondary HPT. Previous studies have shown that the expression of calcium receptor (CaR), calcium-sensing receptor (CAS) and vitamin D recept or (VDR) protein, and mRNA is decreased in hyperplastic parathyroid glands of secondary HPT when compared with normal parathyroid glands. Methods. Thirty-six hyperplastic glands from 18 patients with secondary hyp erparathyroidism were analyzed with in situ hybridization in order to inves tigate the expression of CaR, CAS, VDR, and PTH mRNAs in the same specimens . In nine nodular parathyroid glands, it was possible to make a comparison between the expression of these mRNAs in nodular and internodular areas. Results. The level of CaR was in the same order of magnitude in the hyperpl astic glands and in the biopsies of normal parathyroid, whereas the levels of CAS, VDR and PTH were clearly reduced in the hyperplastic glands. There was a positive correlation between the expression of CaR and CAS (P=0.02). Otherwise, no correlations between CaR, CAS, VDR, and PTH mRNAs were found. The expression of all four genes was highly variable as well between diffe rent glands as within individual glands. Conclusion. The expression of mRNAs for receptors of importance in the cont rol of PTH secretion and parathyroid cell proliferation is heterogeneously decreased in parathyroid glands of secondary HPT. The expression pattern co rroborates earlier studies in which it has been assumed that each nodule in secondary HPT is of monoclonal origin, but that the monoclonal origin of e ach nodule is independent.