title: Hyperparathyroidism of multiple endocrine neoplasia type 1: candidate gene and parathyroid calcium sensing protein expression.
abstract: BACKGROUND
  Hyperparathyroidism affects most patients with multiple endocrine neoplasia type 1 (MEN 1). This study investigates expression of the candidate MEN1 gene phospholipase C beta 3 (PLC beta 3) and expression and function of a putative calcium sensing protein (CAS) in hyperparathyroidism of MEN 1.
  
  
  METHODS
  In 31 parathyroid glands from 17 patients with MEN 1, CAS distribution was studied immunohistochemically and parallel sections were explored for PLC beta 3 mRNA expression by in situ hybridization. Enzymatically dispersed parathyroid cells were analyzed for cytoplasmic calcium concentrations [Ca2+]i and parathyroid hormone (PTH) release.
  
  
  RESULTS
  All glands exhibited a heterogeneously reduced CAS immunoreactivity, especially meager in nodularly assembled parathyroid cells. Calcium regulated [Ca2+]i and PTH release tended to be more deranged in the glands possessing the lowest immunostaining. Parathyroid PLC beta 3 invariably was homogeneously expressed, and this included even MEN 1 patients with reduced PLC beta 3 expression in endocrine pancreatic tumors.
  
  
  CONCLUSIONS
  The findings support variable calcium insensitivity of [Ca2+]i and PTH release in hyperparathyroidism of MEN 1, apparently coupled to heterogeneously reduced CAS expression. For clarification of the role of PLC beta 3 in MEN 1 parathyroid tumorigenesis further study of this protein is required.
mesh_terms: D000328:Adult; D002118:Calcium / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D006961:Hyperparathyroidism / Q000150:complications / Q000235:genetics*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D018761:Multiple Endocrine Neoplasia Type 1 / Q000150:complications / Q000235:genetics*; D010280:Parathyroid Glands / Q000737:chemistry / Q000378:metabolism; D010281:Parathyroid Hormone / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface / Q000032:analysis / Q000235:genetics*; D010738:Type C Phospholipases / Q000032:analysis / Q000235:genetics*
chemical_list: D010281:Parathyroid Hormone; D012333:RNA, Messenger; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface; D010738:Type C Phospholipases; D002118:Calcium