Hyperparathyroidism of multiple endocrine neoplasia type 1: Candidate gene and parathyroid calcium sensing protein expression

Journal Article

Background. Hyperparathyroidism affects most patients with multiple endocrine neoplasia type 1 (MEN 1). This study investigates expression of the candidate MEN 1 gene phospholipase C β3 (PLC β 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 β3 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 β3 invariably was homogeneously expressed, and this included even MEN 1 patients with reduced PLC β3 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 β3 in MEN 1 parathyroid tumorigenesis further study of this protein is required.

Full Text

Duke Authors

Cited Authors

  • Carling, T; Rastad, J; Ridefelt, P; Gobl, A; Hellman, P; Oberg, K; Rask, L; Larsson, C; Juhlin, C; al, E

Published Date

  • 1995

Published In

Volume / Issue

  • 118 / 6

Start / End Page

  • 924 - 931

International Standard Serial Number (ISSN)

  • 0039-6060

Digital Object Identifier (DOI)

  • 10.1016/S0039-6060(05)80095-9