Rat calcium-sensing receptor is regulated by vitamin D but not by calcium

Brown, Alex; Zhong, Min; Finch, Jane; Ritter, Cynthia S.; McCracken, Ruth; Morrissey, Jeremiah J.; Slatopolsky, Eduardo

doi:10.1152/ajprenal.1996.270.3.f454

Cited by 117 publications

(108 citation statements)

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“…The CASR gene has VDREs in the 5 0 -flanking region and is regulated by binding 1,25-dihydroxyvitamin D and VDR complex to VDREs (33,34); thus, the reduction in CASR could be a consequence of reduced VDR. Previously, it has been suggested that reduced CASR expression could be the initiating event in parathyroid tumorigenesis (35). However, it seems more likely that CASR reduction is secondary to reduction in VDR expression as we found a greater magnitude of reduction in VDR compared with CASR expression.…”

Section: Discussioncontrasting

confidence: 43%

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

Varshney

Bhadada

Saikia

et al. 2013

European Journal of Endocrinology

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Background: To explore underlying molecular mechanisms in the pathogenesis of symptomatic sporadic primary hyperparathyroidism (PHPT). Materials and methods: Forty-one parathyroid adenomas from patients with symptomatic PHPT and ten normal parathyroid glands either from patients with PHPT (nZ3) or from euthyroid patients without PHPT during thyroid surgery (nZ7) 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. Results: Immunohistochemistry 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, both VDR and CASR mRNAs were reduced by 0.36-and 0.45-fold change (P!0.001) and CD1 and PTH mRNAs were increased by 9.4-and 17.4-fold change respectively (P!0.001) in adenomatous parathyroid tissue. PTH mRNA correlated with plasma PTH (rZ0.864; P!0.001), but not with adenoma weight, while CD1 mRNA correlated with adenoma weight (rZ0.715; P!0.001). There were no correlations between VDR and CASR mRNA levels and serum Ca, plasma intact PTH, or 25-hydroxyvitamin D levels. In addition, there was no relationship between the decreases in VDR and CASR mRNA expressions and the increases in PTH and CD1 mRNA expressions. Conclusions: The expression of both VDR and CASR are reduced in symptomatic PHPT in Asian Indians. In addition, CD1 expression was greatly increased and correlated with adenoma weight, implying a potential role for CD1 in adenoma growth and differential clinical expression of PHPT.

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Section: Discussioncontrasting

confidence: 43%

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

Varshney

Bhadada

Saikia

et al. 2013

European Journal of Endocrinology

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“…These results are similar to those of Brown et al (1996) who found that CaR mRNA was not regulated by Ca 2+ concentrations, but rather by calcitriol. The effect of calcitriol on CaR mRNA and PTH mRNA expression was not evaluated in this study.…”

Section: Discussionsupporting

confidence: 91%

Parathyroid hormone (PTH) secretion, PTH mRNA and calcium-sensing receptor mRNA expression in equine parathyroid cells, and effects of interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha on equine parathyroid cell function

Toribio¹,

Kohn²,

Capen³

et al. 2003

Journal of Molecular Endocrinology

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Parathyroid hormone (PTH) is secreted by the chief cells of the parathyroid gland in response to changes in ionized calcium (Ca 2+ ) concentrations. In this study, we measured PTH secretion, and PTH mRNA and calcium-sensing receptor (CaR) mRNA expression by equine parathyroid chief cells in vitro. We also evaluated the effects of interleukin (IL)-1 , IL-6, and tumor necrosis factor (TNF)-on PTH secretion, and PTH and CaR mRNA expression. The relationship between PTH and Ca 2+ was inversely related. PTH secretion decreased from 100% (day 0) to 13% (day 30). PTH mRNA expression declined from 100% (day 0) to 25% (day 30). CaR mRNA decreased from 100% (day 0) to 16% (day 30). Chief cells exposed to high (2·0 mM) Ca 2+ concentrations had a lower PTH mRNA expression compared with low Ca 2+ concentrations. Ca 2+ concentrations had no effect on CaR mRNA expression. The inhibitory effect of high Ca 2+ concentrations on PTH secretion also declined over time. After day 10, there was no significant difference in PTH secretion between low and high Ca 2+ concentrations. IL-1 decreased both PTH secretion (75%) and PTH mRNA expression (73%), and resulted in a significant overexpression of CaR mRNA (up to 142%). The effects of IL-1 were blocked by an IL-1 receptor antagonist. IL-1 decreased the Ca 2+ set-point from 1·4 mM to 1·2 mM. IL-6 decreased PTH secretion (74%), but had no effect on PTH and CaR mRNA expression. TNF-had no effect on PTH secretion, and PTH and CaR mRNA expression. In summary, the decreased responsiveness of parathyroid cells to Ca 2+ from 0 to 30 days can be explained, in part, by the reduced CaR expression. IL-1 and IL-6 but not TNF-affected parathyroid function in vitro and may be important in influencing PTH secretion in the septic horse.

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“…Mutations and deletions of the coding region in the CaSR gene do not seem to be involved in this decrease (29,30). The CaSR gene has been demonstrated to have vitamin D-responsive elements (VDREs) in the 5 0 -flanking region and to be regulated by 1,25(OH) 2 D 3 through binding the complex of 1,25(OH) 2 D 3 with VDR to VDREs (31), as has been suggested by an in vivo study of a renal failure model (32). Taken together with our finding of a significant Figure 4 Single regression analyses between Ki67 LI, CaSR and VDR scores in PTGs.…”

Section: Discussionmentioning

confidence: 95%

Decrease in vitamin D receptor and calcium-sensing receptor in highly proliferative parathyroid adenomas

Yano

Sugimoto

Tsukamoto

et al. 2003

European Journal of Endocrinology

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Objective: A significant decrease in vitamin D receptor (VDR) and calcium-sensing receptor (CaSR) protein expression has been demonstrated recently in parathyroid (PT) adenomas. In this study, we investigated the relationships between the proliferative activity of parathyroid glands (PTGs) and the expression of VDR as well as CaSR, and compared it with the clinical severity in patients with primary hyperparathyroidism (18HPT). Design: Seven patients with 18HPT were included in this study. Four patients with thyroid carcinoma served as controls. Methods: Immunohistochemical staining was performed on serial sections of PTGs with specific antibodies against CaSR, VDR, and Ki67. Areas examined in each section were selected at random in relation to the gland size. The number of Ki67-positive cells was expressed as a labeling index (LI; positive cells per 1000 PT cells). The expression of CaSR and VDR was semi-quantitatively analyzed based on the intensity of staining. After averages of the scores from all areas were calculated, CaSR and VDR scores, and Ki67 LI were assigned to each gland for use in statistical analyses. Results: In PT adenomas, scores of VDR and CaSR were markedly lower than in normal PTGs ðP , 0:01Þ; while the proportion of Ki67-positive cells in PT adenomas was significantly higher than in normal PTGs ðP , 0:01Þ: Single regression analyses revealed that Ki67 LI was positively correlated with serum levels of intact parathyroid hormone and Ca, and PTG weight (R ¼ 0:70; P , 0:05; R ¼ 0:78; P , 0:01 and R ¼ 0:84; P , 0:05 respectively). Ki67 LI was negatively correlated with CaSR and VDR scores (R ¼ 20:78; P , 0:01 and R ¼ 20:72; P , 0:05 respectively). Moreover, there was a strong positive relationship between CaSR and VDR expression ðR ¼ 0:95; P , 0:001Þ: Conclusions: Marked decreases in VDR and CaSR expression could, at least in part, be responsible for the high proliferation of PT cells and the pathological progression of 18HPT.

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Rat calcium-sensing receptor is regulated by vitamin D but not by calcium

Cited by 117 publications

References 0 publications

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

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

Parathyroid hormone (PTH) secretion, PTH mRNA and calcium-sensing receptor mRNA expression in equine parathyroid cells, and effects of interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha on equine parathyroid cell function

Decrease in vitamin D receptor and calcium-sensing receptor in highly proliferative parathyroid adenomas

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