Simultaneous expression analysis of vitamin D receptor, calcium-sensing receptor, cyclin D1, and PTH in symptomatic primary hyperparathyroidism in Asian Indians

Abstract

BackgroundTo explore underlying molecular mechanisms in the pathogenesis of symptomatic sporadic primary hyperparathyroidism (PHPT).Materials and methodsForty-one parathyroid adenomas from patients with symptomatic PHPT and ten normal parathyroid glands either from patients with PHPT (n=3) or from euthyroid patients without PHPT during thyroid surgery (n=7) were analyzed for vitamin D receptor (VDR), calcium-sensing receptor (CASR), cyclin D1 (CD1), and parathyroid hormone (PTH) expressions. The protein expressions were assessed semiquantitatively by immunohistochemistry, based on percentage of positive cells and staining intensity, and confirmed by quantitative real-time PCR.ResultsImmunohistochemistry revealed significant reductions in VDR (both nuclear and cytoplasmic) and CASR expressions and significant increases in CD1 and PTH expressions in adenomatous compared with normal parathyroid tissue. Consistent with immunohistochemistry findings, bothVDRandCASRmRNAs were reduced by 0.36- and 0.45-fold change (P<0.001) andCD1andPTHmRNAs were increased by 9.4- and 17.4-fold change respectively (P<0.001) in adenomatous parathyroid tissue.PTHmRNA correlated with plasma PTH (r=0.864;P<0.001), but not with adenoma weight, whileCD1mRNA correlated with adenoma weight (r=0.715;P<0.001). There were no correlations betweenVDRandCASRmRNA levels and serum Ca, plasma intact PTH, or 25-hydroxyvitamin D levels. In addition, there was no relationship between the decreases inVDRandCASRmRNA expressions and the increases inPTHandCD1mRNA expressions.ConclusionsThe expression of both VDR and CASR are reduced in symptomatic PHPT in Asian Indians. In addition,CD1expression was greatly increased and correlated with adenoma weight, implying a potential role for CD1 in adenoma growth and differential clinical expression of PHPT.