Heterogeneous expression of receptor mRNAs in parathyroid glands of secondary hyperparathyroidism.
BACKGROUND
Secondary hyperparathyroidism (HPT) is characterized by inappropriate control of parathyroid hormone (PTH) secretion and asymmetric hyperplasia of the parathyroid glands. Receptors for calcium and vitamin D are involved in the control of secretion, as well as parathyroid cell proliferation. Defective receptor mechanisms therefore may play a role in the pathogenensis of secondary HPT. Previous studies have shown that the expression of calcium receptor (CaR), calcium-sensing receptor (CAS) and vitamin D receptor (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 hyperparathyroidism were analyzed with in situ hybridization in order to investigate 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 hyperplastic 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 different glands as within individual glands.


CONCLUSIONS
The expression of mRNAs for receptors of importance in the control of PTH secretion and parathyroid cell proliferation is heterogeneously decreased in parathyroid glands of secondary HPT. The expression pattern corroborates earlier studies in which it has been assumed that each nodule in secondary HPT is of monoclonal origin, but that the monoclonal origin of each nodule is independent.
Välimäki
S
S
Department of Molecular Medicine, Endocrine Tumor Unit, CMM L8:01, Karolinska Hospital, S-171 76 Stockholm, Sweden. Stiina.Valimaki@cmm.ki.se
Farnebo
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F
Forsberg
L
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Larsson
C
C
Farnebo
L O
LO
D000328:Adult; D000368:Aged; D002135:Calcium-Binding Proteins / Q000235:genetics*; D002648:Child; D005260:Female; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010280:Parathyroid Glands / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis*; D018167:Receptors, Calcitriol / Q000235:genetics*; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface / Q000235:genetics*
D002135:Calcium-Binding Proteins; D010281:Parathyroid Hormone; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases