PMID- 7491535 OWN - NLM STAT- MEDLINE DCOM- 19960104 LR - 20190913 IS - 0039-6060 (Print) IS - 0039-6060 (Linking) VI - 118 IP - 6 DP - 1995 Dec TI - Hyperparathyroidism of multiple endocrine neoplasia type 1: candidate gene and parathyroid calcium sensing protein expression. PG - 924-30; discussion 930-1 AB - 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. FAU - Carling, T AU - Carling T AD - Department of Surgery, University Hospital, Uppsala, Sweden. FAU - Rastad, J AU - Rastad J FAU - Ridefelt, P AU - Ridefelt P FAU - Gobl, A AU - Gobl A FAU - Hellman, P AU - Hellman P FAU - Oberg, K AU - Oberg K FAU - Rask, L AU - Rask L FAU - Larsson, C AU - Larsson C FAU - Juhlin, C AU - Juhlin C FAU - Akerstrom, G AU - Akerstrom G AU - et al. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Surgery JT - Surgery JID - 0417347 RN - 0 (Parathyroid Hormone) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Calcium-Sensing) RN - 0 (Receptors, Cell Surface) RN - EC 3.1.4.- (Type C Phospholipases) RN - SY7Q814VUP (Calcium) SB - IM MH - Adult MH - Calcium/metabolism MH - Female MH - *Gene Expression MH - Humans MH - Hyperparathyroidism/complications/*genetics MH - Immunohistochemistry MH - In Situ Hybridization MH - Male MH - Middle Aged MH - Multiple Endocrine Neoplasia Type 1/complications/*genetics MH - Parathyroid Glands/chemistry/metabolism MH - Parathyroid Hormone/metabolism MH - RNA, Messenger/analysis MH - Receptors, Calcium-Sensing MH - Receptors, Cell Surface/analysis/*genetics MH - Type C Phospholipases/analysis/*genetics EDAT- 1995/12/01 00:00 MHDA- 1995/12/01 00:01 CRDT- 1995/12/01 00:00 PHST- 1995/12/01 00:00 [pubmed] PHST- 1995/12/01 00:01 [medline] PHST- 1995/12/01 00:00 [entrez] AID - S0039-6060(05)80095-9 [pii] AID - 10.1016/s0039-6060(05)80095-9 [doi] PST - ppublish SO - Surgery. 1995 Dec;118(6):924-30; discussion 930-1. doi: 10.1016/s0039-6060(05)80095-9.