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.

• Authors: T Carling, J Rastad, P Ridefelt, A Gobl, P Hellman, K Oberg, L Rask, C Larsson, C Juhlin, G Akerström
• Journal: Surgery (Surgery) Vol. 118 Issue 6 Pg. 924-30; discussion 930-1 (Dec 1995) ISSN: 0039-6060 [Print] United States
• PMID: 7491535 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Parathyroid Hormone
• RNA, Messenger
• Receptors, Calcium-Sensing
• Receptors, Cell Surface
• Type C Phospholipases
• Calcium

Topics

• Adult
• Calcium (metabolism)
• Female
• Gene Expression
• Humans
• Hyperparathyroidism (complications, genetics)
• Immunohistochemistry
• In Situ Hybridization
• Male
• Middle Aged
• Multiple Endocrine Neoplasia Type 1 (complications, genetics)
• Parathyroid Glands (chemistry, metabolism)
• Parathyroid Hormone (metabolism)
• RNA, Messenger (analysis)
• Receptors, Calcium-Sensing
• Receptors, Cell Surface (analysis, genetics)
• Type C Phospholipases (analysis, genetics)