Molecular Analysis of Glucocorticoid Receptors in Patients with Familial Cortisol Resistance
| Project/Area Number |
01570638
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
内分泌・代謝学
|
|---|
| Research Institution | Osaka University |
|---|
Principal Investigator |
IIDA Sayomi Osaka Univ. Medicine Assistant Teacher, 医学部, 助手 (40159554)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
MORIWAKI Kaname Osaka Univ. Medicine Associate Prof., 医学部, 助教授 (90028548)
|
|---|
| Project Period (FY) |
1989 – 1990
|
| Project Status |
Completed (Fiscal Year 1990)
|
| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1990: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1989: ¥1,300,000 (Direct Cost: ¥1,300,000)
|
|---|
| Keywords | Cortisol resistance / Glucocorticoid Receptor / Cortisol / Hypercortisolemia / Cushing's syndrome / Fibroblast / Lymphocyte / Glucocorticoid / デキサメサゾン / グルココルチコイド受容体遺伝子 / 家族性コルチゾ-ル抵抗症 / EBーvirus transformed lymphocytes / 受容体測定 / 異常グルココルチコイド受容体 |
|---|
| Research Abstract |
We have previously reported a family with primary cortisol resistance. Two patients from this family have sustained hypercortisolemia without any signs or symptoms of Cushing's syndrome. We demonstrated that glucocorticoid receptor (GR) levels in these patients are reduced to one half of normal controls by binding assays using peripheral mononuclear leukocytes, cultured skin fibroblasts and Epstein-Barr virus-transformed lymphocytes. GR protein was analyzed by Western blot using an antibody against the C-terminal portion of the rat GR. The patients' cells had GR immunoreactivities at the same positions as the controls, but the intensities appeared to be reduced in the patients. Northern analysis of GR mRNA revealed a 7kb band both in the patients and controls ; but in spite of the reduced GR binding and protein levels, the quantity of GR mRNA was normal in the patients' cells. Thus, we excluded the possibilities that the size or quantity of GR mRNA is abnormal in the patients. To characterize the GR mRNA, RNase protection assays were conducted. Regions of mRNA corresoponding to DNA binding domains and steroid binding domains were protected in the patients' cells as well as the controls. These results suggest that the patients have inherited one normal GR gene and one mutated gene which results in synthesis of a smaller truncated GR protein lacking the antibody recognition site.
|
Report
(3 results)
Research Products
(15 results)
