1999 Fiscal Year Final Research Report Summary
Pathophysiologic mechanisms of the abnormal parathyroid hormone secretion
| Project/Area Number |
09470223
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
内分泌・代謝学
|
|---|
| Research Institution | OKAYAMA UNIVERSITY |
|---|
Principal Investigator |
SEINO Yoshiki Okayama University Medical School, Professor, 医学部, 教授 (80028620)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
INOUE Masaru Okayama University Medical School, Hospital, Lecturer, 医学部・附属病院, 講師 (20253023)
TANAKA Hiroyuki Okayama University Medical School, Hospital, Lecturer, 医学部・附属病院, 講師 (80231413)
|
|---|
| Project Period (FY) |
1997 – 1999
|
| Keywords | secondary hyperparathyroidism / calcium sensing receptor / polymorphism / intracellular calcium / inositol tris phosphate |
|---|
| Research Abstract |
The management of secondary hyperparathyroidism and renal osteodystrophy in end-stage renal failure is an important clinical problem. For the development of new and ideal methodologies, it is essential to know the pathophysiologic mechanisms of the parathyroid hormone secretion and the parathyroid cellular proliferation. To this aid, we have investigated the function of the calcium sensing receptor (Casr).
We have already identified several mutations in neonatal severe hyperparathyroidism. To clarify the function of these mutant Casr, the mutants produced by site directed mutagenesis were expressed in HEK 293 cell and the response to the change in extracellular calcium concentration was evaluated by measuring intracellular calcium concentration and inositol tris phosphate production. In these experiments, we confirmed that these mutants were functionless. This result in hands, we next explored the effects of Casr in the cellular proliferation and the effects of extracellular conditions on the function of the receptor. The results clearly indicated the close relationship between the function of receptor and the cellular proliferation, and suggested importance of the extracellular glucose concentration in its function. Moreover, we identified close relationship between the genetic polymorphism in the Casr gene and the severity of the secondary hyperparathyroidism.
|
