1995 Fiscal Year Final Research Report Summary
Gene regulation by thyroid hormone
| Project/Area Number |
05670868
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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 | Kochi Medical School |
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Principal Investigator |
TAKEDA Kyoko Kochi Medical School, Clinical Laboratory Medicine Assistant Prutessor, 医学部, 講師 (30243827)
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| Co-Investigator(Kenkyū-buntansha) |
OKABAYASHI Tomoaki Kochi Medical School, 2nd Dep.of Medicine Assistant, 医学部, 助手 (70274371)
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| Project Period (FY) |
1993 – 1995
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| Keywords | Thyroid Hormone / Sex Hormone Binding Ghobulr / Choning / Promoter |
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| Research Abstract |
The levels of serum sex hormone binding globulin (SHBG) were significantly correlated with serum free thyroxine concentrations in panients with hyper- and hypothyroidism as well as in normal healthy subjects. Serum SHBG levels were also elevated in patients with automomous functioning thyroid nodules (AFTN) to compared with those of sex- and age- matched healthy controls. Serum SHBG concentrations were decreased following surgical removal of the nodule, with the magnitude of the decrease proportional to the decrease in serum thyrocxine. These results are consistent with a direct effect of thyroid hormone on SHBG exprssion. Since thyroid hormone exerts its biological effects by increasing or decreasing transcription, we have cloned the promoter region of human SHBG gene as a first step in studying the transcriptional regulation of SHBG by thyroid hormone. A human cosmid library in the vector Lorist 2 was screened by hybridization using as probes 32P-labeled oligonucleotides (P1,32mer ;
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P2,33mer) specific for exons 1 and 1'. Seven positively hybridizing clones were identified. The results of Southern blotting suggested that the clones phSHBG-2 and 5 contained regions of the promoter of different size. Cosmid mapping confirmed the Southern blotting results and showed that phSHBG-5 contained more promoter region than did phSHBG-2. Subclones (phSHBG-80 and -82) containing different regions of the promoter have generated by digestion of phSHBG-5 with the resriction endonuclesaes Hind III and Bam HI,respecitively. Restriction mapping suggests that phSHBG-80 and -82 contain the transcriptional start site of the SHBG gene and 3Kb and 3.7Kb, respectively. Other suclones (phSHBG-H1, -H2 and phSHBG-B1) containing different promoter regions far from the transcriptional start site have generated by digestion of phSHBG-5 with Hind III and Bam HI,respectively. Restriction mapping suggests that phSHBG-H1, -H2 and phSHBG-B1 contain 2.2Kb, 4.4kB and 6.5Kb, respectively. These clones will be used as a focus for detailed characterization of the human SHBG gene promoter. Less
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