1998 Fiscal Year Final Research Report Summary
Research on signal transduction through parathyroid hormone(PTH)/PTH-related protein receptor
| Project/Area Number |
09671030
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
内分泌・代謝学
|
|---|
| Research Institution | The University of Tokyo |
|---|
Principal Investigator |
FUKUMOTO Seiji Department of Laboratory Medicine, The University of Tokyo Branch Hospital, Lecturer, 医学部・附属病院分院, 講師 (30202287)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TAKEUCHI Yasuhiro Department of Medicine, The University of Tokyo Branch Hospital, Assistant Profe, 医学部・附属病院分院, 助手 (50202164)
|
|---|
| Project Period (FY) |
1997 – 1998
|
| Keywords | PTH / PTHrP receptor / Pseudohypoparathyroidism / Calcium-sensing receptor |
|---|
| Research Abstract |
1. Regulation of expression of PTH/PTH-related protein (PTHrP) receptor
In order to clarify the regulatory mechanisms of the expression of PTH/PTHrP receptor, we have cloned and analyzed 5'-region of human PTH/PTHrP receptor gene. The results indicate that human PTH/PTHrP receptor gene has at least two promoters and three 5'-untranslated exons. One of these promoters is specific for kidney, and the other promoter is widely used in many tissues (Fukumoto S et al, 1997).
2. Evaluation of PTH/PTHrP receptor gene in patients with pseudohypoparathyroidism type Ib
Pseudohypoparathyroidism is a heterogenous disease complex characterized by resistance to PTH.Pseudohypoparathyroidism type Ib had been thought to be caused by abnormal PTH/PTHrP receptor. However, previous our results showed that there is no abnormality in cDNA for PTH/PTHrP receptor in these patients (J Clin Endocrinol Metab 81 : 2554,1996). Therefore, we next investigated if the regulatory mechanisms of the expression of PTH/PTHrP receptor is abnormal in these patients. However, promoter regions and 5'-untranslated exons in 8 patients with pseudohypoparathyroidism type Ib showed no abnormality. Together with the recent findings that the responsible gene for pseudohypoparathyroidism type Ib is not located in PTH/PTHrP receptor locus and inactivating mutations of PTH/PTHrP receptor result in Bromstrand chondrodysplasia, it is concluded that pseudohypoparathyroidism type Ib is not caused by abnormal PTH/PTHrP receptor.
3. Study on signal transduction through PTH/PTHrP receptor
Signal transduction through PTH/PTHrP receptor is modulated not only by its expression, but also by the production and secretion dynamics of its ligand. Parathyroid calcium-sensing receptor plays pivotal roles in the regulation of PTH secretion. We have analyzed calcium-sensing receptor gene in several patients with abnormal PTH secretion, and found novel mutations in this receptor gene.
|
-
-
-
-
-
[Publications] Okazaki R,Chikatsu N,Nakatsu M,Takeuchi Y,Ajima M,Miki J,Fujita T,Arai M,Totsuka Y,Tanaka K,Fukumoto S: "A novel activating mutation in calcium-sensing receptor gene associated with a family of autosomal dominant hypocalcemia." J Clin Endocrinol Metab. 84(1). 363-366 (1999)
Description
「研究成果報告書概要(欧文)」より
-
