Decreased calcium-sensing receptor (CaSR) has been observed in hyperparathyroidism (HPT) without a known mechanism. The purpose of this study was to evaluate the expression of CaSR in primary (PHPT) and secondary (SHPT) subtypes. Immunohistochemical (IHC) staining and quantitative real-time PCR (qRT-PCR) assay were used to measure the differences in expression of CaSR protein and gene in PHPT and SHPT human samples, compared to matched controls. CaSR protein was differentially downregulated in SHPT and PHPT compared to normal parathyroid tissues (2.42 ± 0.5 vs. 3.2 ± 0.62, P < 0.05; 1.8 ± 0.83 vs. 3.2 ± 0.62, P < 0.05, respectively). Furthermore, SHPT tissues exhibited significantly higher levels of CaSR mRNA (0.29 ± 0.23 vs. 0.01 ± 0.12, P < 0.05) and protein (2.42 ± 0.5 vs. 1.8 ± 0.83, P < 0.05) than those in PHPT tissue samples. Depressed CaSR expression was a critical pathological hallmark of HPT. We found a differential decline of CaSR, in terms of both mRNA and protein levels, in PHPT and SHPT human samples. We think that CaSR dysregulation occurred at the very beginning of disease onset in PHPT, while a similar pathological scenario appeared at the later stage of SHPT. Future studies should be directed to dissect the mechanistic involvement of CaSR in PHPT and SHPT in order to bring treatment precisions in HPT management.
Objective To study the protein and mRNA expressions of regulator of G-protein signaling 5 (RGS5) in the pathogenesis of hyperparathyroidism. Methods The expression of RGS5 protein in 20 primary hyperparathyroidism (PHPT), 31 secondary hyperparathyroidism (SHPT), and 20 control cases were studied by immunohistochemistry (IHC). The expression of RGS5 mRNA in 15 PHPT, 102 SHPT, and 7 normal parathyroid tissue were measured by quantitative real-time PCR (qRT-PCR) method. Results The expressions of RGS5 in PHPT tissues were significantly higher than that in SHPT and normal parathyroid tissues ( P < 0.05). While the differences in RGS5 protein expressions between SHPT and respective control samples were not statistically significant ( P > 0.05). Likewise, the RGS5 mRNA expression in PHPT was significantly higher than that in SHPT ( P < 0.05) and normal parathyroid ( P < 0.05) samples. In a similar line, the differences in RGS5 gene expressions between SHPT and control tissues were not statistically significant ( P > 0.05). Conclusions The characteristic RGS5 protein and mRNA levels in hyperparathyroidism might be helpful in discovering the pathomechanism of hyperparathyroidism and novel therapeutic targets as well.
Background: Calcium-sensitive receptor (CASR) plays an important role in the pathogenesis and progression of secondary hyperparathyroidism (SHPT). The purpose of this study is to examine the protein and gene expression characteristics of CASR in SHPT.Methods: Immunohistochemistry and real-time PCR were used to detect and compare the expression of CASR protein and genes in SHPT and primary hyperparathyroidism (PHPT) tissues.Results: CASR protein was down-regulated in SHPT and PHPT compared with normal parathyroid tissues (2.42±0.5 vs. 3.2±0.62, P<0.05; 1.8±0.83 vs. 3.2±0.62, P<0.05). Further, SHPT tissue showed higher expression of both CASR protein (2.42±0.5 vs. 1.8±0.83, P<0.05) and CASR gene (0.29±0.23 vs. 0.01±0.12, P<0.05) than PHPT tissue, respectively.Conclusion: The expression of CASR protein and gene in SHPT is higher than that in PHPT. This feature provides a theoretical basis and further ideas for studying the mechanism of CASR down-regulation.