Project/Area Number |
02670426
|
Research Category |
Grant-in-Aid for General Scientific Research (C)
|
Allocation Type | Single-year Grants |
Research Field |
Pediatrics
|
Research Institution | Chiba University |
Principal Investigator |
NIIMI Hiroo Chiba Univ., Medicine, Prof., 医学部, 教授 (40009147)
|
Co-Investigator(Kenkyū-buntansha) |
TAMARU Jyunichi Chiba Univ., Medicine, Assistar, 医学部, 助手 (30188429)
WATAKI Kunio Chiba Univ., Medicine, Resident, 医学部附属病院, 医員
KONDA Susumu Chiba Univ., Medicine, Resident, 医学部附属病院, 医員
MURATA Atushi Chiba Univ., Medicine, Resident, 医学部附属病院, 医員
YASUDA Toshiyuki Chiba Univ., Medicine, Lecturer, 医学部, 講師 (00211615)
|
Project Period (FY) |
1990 – 1991
|
Project Status |
Completed (Fiscal Year 1991)
|
Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1991: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1990: ¥1,700,000 (Direct Cost: ¥1,700,000)
|
Keywords | GH receptor / GH binding protein / IGF-I / IGFーI / 成長ホルモン / 受容体 / ステロイドホルモン / 女性ホルモン / IGF |
Research Abstract |
To clarify the role of peripheral GH receptor expression in the normal linear bone growth as well as in the abnormal conditions such as estrogen excess or thyroid hormone deficiency, we have developed 1) the method to determine GH binding protein activity in the sera by both gel filtration and immunoprecipitation using Mab263 2) the antibodies to synthetic peptides based on the reported human GH receptor amino acid sequence 3) the method to analyze IGFBPs and 4) the method to detect GH receptor immunohistochemically. 1 : GHBP in the human sera was shown to correspond to the extracellular domain of GH receptor. GHBP activity in two assay systems was very low in the cord blood, and rose rapidly with age. The increase in GHBP with age was very similar to that in IGFI, therefore, there is a significant correlation between GHBP and IGFI in children under 10 y. The reduction in the GHBP was shown in patients with anorexia nervosa, which was normalized by an improved nutritional state. This may indicate a reduction in growth hormone (GH) receptors in this condition resulting in low insulin-like growth factor I (IGF-I) production. 2 : GHBP activities tended to be low in children with sexual precocity which increased with a suppression of estrogen secretion. Hyper- or hypothyroidism seemed not to affect GHBP. To further clarify our results, our current investigation addresses how these changes are controlled with respect to GH receptor in the tissue as well as in the transcriptional regulation of GH receptor gene including alternative use of exons.
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