Abstract. The parathormone (PTH) production is controlled by calcium and vitamin D, which interact with the calciumsensing receptor (CaSR) and vitamin D receptor (VDR), respectively. All of these elements control calcium homeostasis, which is crucial for many physiological processes. Thus, impairment of the upstream component of this system, e.g. a decrease of CaSR and/or VDR, could result in hyperparathyroidism (HPTH). Therefore, the aim of this study was to assess the expression of CaSR and VDR in a tertiary form of HPTH (T-HPTH). The study involved 19 T-HPTH patients qualified for parathyroidectomy and 21 control parathyroids harvested from multi-organ cadaver donors. The small fragments of harvested glands were homogenized and used for Western blot analysis, whereas the remaining tissues underwent routine hematoxylin-eosin staining or immunostaining for CaSR and VDR. Among 64 T-HPTH parathyroids, 58 revealed the morphology of benign hyperplasia, 2 were identified as adenoma and 4 were classified as normal; some glands displayed a mixed histological phenotype. Western blot analysis revealed a decrease of CaSR and VDR in hyperplasia and adenomaderived samples. However, no correlation between the types of hyperplasia and receptor expression was observed. On the other hand, microscopic analysis of CaSR-and VDRimmunostained sections revealed a highly differentiated and significantly decreased mean expression of both receptors, which correlated with parathyroid histology. The reason behind the impaired expression of CaSR and VDR in T-HPTH is unclear. It presumably results from constant parathyroid stimulation at the stage of S-HPTH, followed by further development of polyclonal autonomy. However, the verification of this thesis requires further study.
IntroductionThe production and secretion of parathormone (PTH), a main hormone produced by chief cells of parathyroid glands, remains under the control of calcium ions and vitamin D metabolites. The target molecules for these two key regulatory factors are calcium-sensing receptor (CaSR) and vitamin D receptor (VDR), respectively (1).Calcium-sensing receptor, which belongs to the class III of G-protein coupled receptors, could be activated by various di-and tri-valent cations, especially Ca 2+ and Mg 2+ , but also L-amino acids and other positively charged molecules (2). The triggering of CaSR by these agonists has been shown to post-transcriptionally down-regulate PTH expression, primarily by influencing the PTH-mRNA stability (1). The activation of CaSR also appears to inhibit parathyroid cell proliferation, however, the detailed molecular mechanism of this action remains unclear (3). Presumably, a useful model for the more precise determination of CaSR biological significance could be patients with loss-of-function receptor mutations, resulting in familial benign (hypocalciuric) hypercalcaemia (FBHH) or neonatal severe primary hyperparathyroidism (NSP-HPTH) (4).The receptor for vitamin D is the intracellular phosphoprotein belonging to the nuclear receptor superfa...