HYPERPARATHYROIDISM OF MULTIPLE ENDOCRINE NEOPLASIA TYPE-1 - CANDIDATE GENE AND PARATHYROID CALCIUM SENSING PROTEIN EXPRESSION

Background. Hyperparathyroidism affects most patients with endocrine n eoplasia type 1 (MEN 1). This study investigates expression of the can didate MEN1 gene phospholipase C beta 3 (PLC beta 3) and expression an d function of a putative calcium sensing protein (CAS) in hyperparathy roidism of MEN 1. Methods. In 31 parathyroid glands from 17 patients w ith MEN 1, CAS distribution was studied immunohistochemically and para llel 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 horm one (PTH) release. Results. All glands exhibited a heterogeneously red uced CAS immunoreactivity, especially meager in nodularly assembled pa rathyroid 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 thi s included even MEN 1 patients with reduced PLC beta 3 expression in e ndocrine pancreatic tumors. Conclusions. The findings support variable calcium insensitivity of [Ca2+](i) and PTH release in hyperparathyroi dism of MEN 1, apparently coupled to heterogeneously reduced CAS expre ssion. for clarification of the role of PLC beta 3 in MEN 1 parathyroi d tumorigenesis further study of this protein is required.