title: Simultaneous expression analysis of vitamin D receptor, calcium-sensing receptor, cyclin D1, and PTH in symptomatic primary hyperparathyroidism in Asian Indians.
abstract: BACKGROUND
  To explore underlying molecular mechanisms in the pathogenesis of symptomatic sporadic primary hyperparathyroidism (PHPT).
  
  
  METHODS
  Forty-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.
  
  
  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 (r=0.864; P<0.001), but not with adenoma weight, while CD1 mRNA correlated with adenoma weight (r=0.715; 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.
authors: Department of Endocrinology, Postgraduate Institute of Medical Education and Research, 4th Floor, F-Block, Room No. 2, Chandigarh 160012, India.
authors: Shweta
authors: S
authors: Varshney
authors: Sanjay Kumar
authors: SK
authors: Bhadada
authors: Uma Nahar
authors: UN
authors: Saikia
authors: Naresh
authors: N
authors: Sachdeva
authors: Arunanshu
authors: A
authors: Behera
authors: Ashutosh Kumar
authors: AK
authors: Arya
authors: Sadhna
authors: S
authors: Sharma
authors: Anil
authors: A
authors: Bhansali
authors: Ambrish
authors: A
authors: Mithal
authors: Sudhaker D
authors: SD
authors: Rao
mesh_terms: D000236:Adenoma / Q000737:chemistry*; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D019938:Cyclin D1 / Q000032:analysis* / Q000235:genetics; D018076:DNA, Complementary / Q000138:chemical synthesis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D049950:Hyperparathyroidism, Primary / Q000378:metabolism*; D007150:Immunohistochemistry; D007194:India; D008297:Male; D008875:Middle Aged; D010280:Parathyroid Glands / Q000737:chemistry*; D010281:Parathyroid Hormone / Q000032:analysis* / Q000235:genetics; D010282:Parathyroid Neoplasms / Q000737:chemistry*; D012333:RNA, Messenger / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D018167:Receptors, Calcitriol / Q000032:analysis* / Q000235:genetics; D044169:Receptors, Calcium-Sensing / Q000032:analysis* / Q000235:genetics; D015854:Up-Regulation; D044465:White People
chemical_list: D018076:DNA, Complementary; D010281:Parathyroid Hormone; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D044169:Receptors, Calcium-Sensing; D019938:Cyclin D1