1992 Fiscal Year Final Research Report Summary
Molecular Analysis of Glucocorticoid Receptors in Patients with Familial Cortisol Resistence
| Project/Area Number |
03671149
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
内分泌・代謝学
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| Research Institution | Osaka University |
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Principal Investigator |
NAMBA Mitsuyoshi OSAKA UNIV. MEDICINE ASSISTENT TEACHER, 医学部, 助手 (00183533)
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| Co-Investigator(Kenkyū-buntansha) |
FUJII Hiroshi OSAKA UNIV. MEDICINE SENIOR REGISTRAR, 医員
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| Project Period (FY) |
1991 – 1992
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| Keywords | Cortisol resistence / Glucocorticoid receptor / Cortisol / Cushing syndrome / Hypercortisolemia / Fibroblast / Lymphocyte / Epstein-Barr virus |
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| Research Abstract |
We have previously reported two patients in the same family with primary cortisol resistance accompanied by a decrease in numbers of glucocorticoid receptors (GR) in peripheral mononuclear cells. These patients, patient I (35-year-old male) and patient II (mother), had sustained hypercortisolemia, but they presented no manifestation of Cushing's syndrome. Both patients exhibited mild hypertension without hypokalemia. They were partially resistant to dexamethasone adrenal suppression. Reduced numbers but normal affinity of GR were also found in Epstein-Barr virus (EBV) - transformed lymphocytes. Total RNA was isolated from the EBV-transformed lymphocytes. Single-stranded cDNA was synthesized from total RNA by a reverse transcription reaction. GR cDNA from both patients was ampli. fied by polymerase chain reaction. Direct sequencing of PCR products revealed a three base-pair (AAA) deletion at codon 2443. Both patients were heterozygous for the deletion. The deletion results in the loss of a lysine residue in the steroid-binding domain of the GR.
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