| Project/Area Number |
09671030
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
内分泌・代謝学
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| Research Institution | The University of Tokyo |
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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)
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| 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)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1997: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | PTH / PTHrP receptor / Pseudohypoparathyroidism / Calcium-sensing receptor / Ca感知受容体 / 副甲状腺ホルモン受容体 / プロモーター |
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| 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.
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