1996 Fiscal Year Final Research Report Summary
STUDY ON THE MOLECULAR MECHANISM OF GLUCOCORTICOID HORMONE ACTION
| Project/Area Number |
07671099
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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 | ASAHIKAWA MEDICAL COLLEGE |
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Principal Investigator |
TANAKA Hirotoshi ASAHIKAWA MEDICAL COLLEGE,SECOND DEPARTMENT OF INTERNAL MEDICINE,ASSISTANT PROFESSOR OF MEDICINE, 医学部, 講師 (00171794)
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| Project Period (FY) |
1995 – 1996
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| Keywords | glucocorticoids / transcription factors / DNA binding protein / molecular biology / endocrinology / redox |
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| Research Abstract |
The molecular mechanisms of glucocorticoid hormone action were studied with special reference to
1) regulation of glucocorticoid receptor expression.
2) interplay between the glucocorticoid receptor and transcription factors,
3) functional significance of post-translational modification of the glucocorticoid receptor.
1) Expression of the glucocorticoid receptor was negatively modulated by agonistic ligands, and this down-regulation of the glucocorticoid receptor was correlated with down-modulation of hormone responsiveness.
2) Interaction between the glucocorticoid receptor and CREB and AP-1 was biochemically characterized. Moreover, clinical importance of such factor interaction was clearly demonstrated by using thyroid cells and fibroblasts as model systems.
3) Redox-regulation of the glucocorticoid receptor was investigated. The cysteine residues of the receptor was shown to susceptible to oxidative stress, and thioredoxin, as an electron donor, potentiated the receptor mediated gene expression.
Together, the molecular understanding of hormone action was extensively advanced.
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