title: Exclusive underexpression of vitamin D receptor exon 1f transcripts in tumors of primary hyperparathyroidism.
abstract: OBJECTIVE
  Primary hyperparathyroidism (pHPT) is characterized by excessive production of parathyroid hormone (PTH) due to parathyroid adenomas while uremic secondary HPT (sHPT) is caused by parathyroid hyperplasia in response to renal failure. Active vitamin D, 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)), with the vitamin D receptor (VDR) is involved in regulation of the calcium homeostasis together with PTH. In a feedback loop, 1,25-(OH)(2)D(3) has a direct action on the parathyroid gland to regulate PTH transcription, PTH secretion and cell proliferation. We have previously demonstrated reduced VDR mRNA expression in parathyroid adenomas and hyperplasia of sHPT using a probe detecting all 14 variant VDR transcripts expressed in parathyroid cells. Here we have assessed which of the 5'-terminal exon 1a, 1d and 1f variant VDR transcripts are reduced in pathological parathyroid glands.
  
  
  METHODS
  The relative VDR/glyceraldehyde-3-phosphate dehydrogenase mRNA levels for each VDR exon were determined by real-time quantitative RT-PCR in five normal parathyroid glands, seventeen parathyroid adenomas and ten hyperplastic glands of sHPT.
  
  
  RESULTS
  The results demonstrated exclusive underexpression of VDR exon 1f transcripts in parathyroid adenoma, while all measured VDR transcripts were reduced in secondary hyperplasia.
  
  
  CONCLUSIONS
  We suggest that exclusive underexpression of VDR exon 1f transcripts in adenomas of pHPT, which derive from a distal promoter active in tIssues involved in calcium regulation by 1,25-(OH)(2)D(3), may either reflect a defective cell type-specific transcription factor or other physiologically important pathway(s) for tIssue-specific VDR gene expression.
authors.affiliation: Department of Surgical Sciences, Endocrine Unit, Uppsala University Hospital, SE-751 85 Uppsala, Sweden.
authors.forename: Pamela
authors.initials: P
authors.lastname: Correa
authors.forename: Goran
authors.initials: G
authors.lastname: Akerstrom
authors.forename: Gunnar
authors.initials: G
authors.lastname: Westin
mesh_terms: D000236:Adenoma / Q000150:complications / Q000378:metabolism*; D000368:Aged; D005091:Exons / Q000235:genetics*; D005260:Female; D006801:Humans; D006961:Hyperparathyroidism / Q000209:etiology*; D006965:Hyperplasia; D008297:Male; D008875:Middle Aged; D010279:Parathyroid Diseases / Q000378:metabolism / Q000473:pathology; D010280:Parathyroid Glands / Q000378:metabolism / Q000473:pathology; D010282:Parathyroid Neoplasms / Q000150:complications / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D018167:Receptors, Calcitriol / Q000235:genetics*; D012016:Reference Values
chemical_list: D012333:RNA, Messenger; D018167:Receptors, Calcitriol