The calcium-sensing receptor and vitamin D receptor expression in tertiary hyperparathyroidism.
The parathormone (PTH) production is controlled by calcium and vitamin D, which interact with the calcium-sensing 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 adenoma-derived samples. However, no correlation between the types of hyperplasia and receptor expression was observed. On the other hand, microscopic analysis of CaSR- and VDR-immunostained 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.
Grzela
Tomasz
T
Cell Molecular Biology Laboratory, Department of Histology and Embryology, Biostructure Research Center, Warsaw Medical University, PL 02 004 Warsaw, Poland. tgrzela@op.pl
Chudzinski
Witold
W
Lasiecka
Zofia
Z
Niderla
Justyna
J
Wilczynski
Grzegorz
G
Gornicka
Barbara
B
Wasiutynski
Aleksander
A
Durlik
Magdalena
M
Boszczyk
Anna
A
Brawura-Biskupski-Samaha
Robert
R
Dziunycz
Piotr
P
Milewski
Lukasz
L
Lazarczyk
Marta
M
Lazarczyk
Maciej
M
Nawrot
Ireneusz
I
D000328:Adult; D015153:Blotting, Western; D005260:Female; D006801:Humans; D006961:Hyperparathyroidism / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010280:Parathyroid Glands / Q000737:chemistry / Q000473:pathology; D018167:Receptors, Calcitriol / Q000032:analysis / Q000096:biosynthesis*; D044169:Receptors, Calcium-Sensing / Q000032:analysis / Q000096:biosynthesis*
D018167:Receptors, Calcitriol; D044169:Receptors, Calcium-Sensing