Reduced vitamin D receptor expression in parathyroid adenomas: implications for pathogenesis

Rao, Sudhaker D; Han, Sang-Min; Phillips, E.; Palnitkar, Saroj; Parfitt,

doi:10.1046/j.1365-2265.2000.01081.x

Cited by 55 publications

(31 citation statements)

References 43 publications

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“…The downregulation of VDR expression in parathyroid adenomas in patients with symptomatic PHPT is similar to previous report of probably mild PHPT patients (12). Because the normal parathyroid tissues in our samples showed both nuclear and cytoplasmic positivity, we separately assessed nuclear and cytoplasmic VDR expression and found decreased expression of VDR at both cellular locations in parathyroid adenomas.…”

Section: Discussionsupporting

confidence: 63%

“…Representative paraffin blocks were retrieved and immunostained as previously reported (12,22) RNA extraction and cDNA synthesis Briefly, each tissue sample was crushed in 1 ml TRI reagent (Sigma-Aldrich). After chloroform addition, the aqueous and organic phases were separated by centrifugation.…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…Abnormalities in VDR (12,13,14), CASR (14,15,16,17,18), and CD1 (19,20,21,22,23) expression have been reported in the cases probably having mild form of PHPT, parathyroid cancers, and renal secondary hyperparathyroidism. However, very little is known about such abnormalities in adenomas from patients with symptomatic sporadic PHPT (24,25,26).…”

Section: Introductionmentioning

confidence: 99%

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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: Discussionsupporting

confidence: 63%

Section: Immunohistochemistrymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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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“…Initial reports showed that vitamin D uptake was higher in parathyroid adenomas compared to cases of secondary hyperplasia and that VDR levels were similar in adenomas compared to normal tissue (Korkor, 1987, Trydal et al, 1992. More recent studies showed reduced levels of VDR mRNA in parathyroid adenomas and reduced immunostaining (Carling et al, 2000, Sudhaker Rao et al, 2000. In our series, mean VDR mRNA levels (as determined by quantitative RT-PCR) did not differ significantly between the three groups.…”

Section: Altered Expression Of Vdr Target Genes In Men1 Parathyroid Asupporting

confidence: 42%

“…VDR null or 1-hydroxylase null (unable to synthesize 1,25(OH) 2 D 3 ) mice develop parathyroid hyperplasia (Bouillon et al, 2008). VDR gene polymorphisms are associated with primary hyperparathyroidism and alterations of VDR mRNA and protein levels have been reported to occur in parathyroid adenomas (Carling et al, 1995, Carling et al, 2000, Sudhaker Rao et al, 2000. Parathyroid adenomas are the most common manifestation of MEN1, with a penetrance of almost 100%.…”

Section: Introductionmentioning

confidence: 99%

Regulation of vitamin D receptor function in MEN1-related parathyroid adenomas

Dreijerink

Varier

Nuland

et al. 2009

Molecular and Cellular Endocrinology

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Multiple endocrine neoplasia type 1 (MEN1) is heriditary syndrome characterised by the occurrence of parathyroid, gastroenteropancreatic and pituitary tumours. The MEN1 gene product, menin, co-activates gene transcription by recruiting histone methyltransferases for lysine 4 of histone H3 (H3K4). We investigated whether in MEN1 tumours global changes in H3K4 trimethylation (H3K4me3) occur or whether alterations in gene expression can be observed. By immunohistochemistry we found that global levels of H3K4me3 are not affected in MEN1-related parathyroid adenomas. Menin can interact directly with the vitamin D receptor (VDR) and enhance the transcriptional activity of VDR. Messenger RNA levels of VDR target genes CYP24 and KLK6 were significantly lower in MEN1 parathyroid adenomas compared to normal tissue. Thus, aberrant gene expression in MEN1 tumours is not caused by lower global H3K4me3, but rather by specific effects on genes that are regulated by menininteracting proteins, such as VDR.

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PTH and Vitamin D

Khundmiri

Murray

Lederer

2016

Comprehensive Physiology

227

158

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PTH and Vitamin D are two major regulators of mineral metabolism. They play critical roles in the maintenance of calcium and phosphate homeostasis as well as the development and maintenance of bone health. PTH and Vitamin D form a tightly controlled feedback cycle, PTH being a major stimulator of vitamin D synthesis in the kidney while vitamin D exerts negative feedback on PTH secretion. The major function of PTH and major physiologic regulator is circulating ionized calcium. The effects of PTH on gut, kidney, and bone serve to maintain serum calcium within a tight range. PTH has a reciprocal effect on phosphate metabolism. In contrast, vitamin D has a stimulatory effect on both calcium and phosphate homeostasis, playing a key role in providing adequate mineral for normal bone formation. Both hormones act in concert with the more recently discovered FGF23 and klotho, hormones involved predominantly in phosphate metabolism, which also participate in this closely knit feedback circuit. Of great interest are recent studies demonstrating effects of both PTH and vitamin D on the cardiovascular system. Hyperparathyroidism and vitamin D deficiency have been implicated in a variety of cardiovascular disorders including hypertension, atherosclerosis, vascular calcification, and kidney failure. Both hormones have direct effects on the endothelium, heart, and other vascular structures. How these effects of PTH and vitamin D interface with the regulation of bone formation are the subject of intense investigation.

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Reduced vitamin D receptor expression in parathyroid adenomas: implications for pathogenesis

Cited by 55 publications

References 43 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

Regulation of vitamin D receptor function in MEN1-related parathyroid adenomas

PTH and Vitamin D

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