2006 Fiscal Year Final Research Report Summary
Investigation of a novel pathogenesis of thrombosis-regulation of protein S by sex hormones and its abnormality-
| Project/Area Number |
16590910
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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 |
Endocrinology
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| Research Institution | Kyushu University |
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Principal Investigator |
OHNAKA Keizo Kyushu University, Graduate Scholl of Medical Sciences, Assistant Professor (30325518)
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| Co-Investigator(Kenkyū-buntansha) |
HAMASAKI Naotaka KYUSHU UNIVERSITY, Graduate School of Medical Sciences, Professor (00091265)
TAKAYANAGI Ryoichi KYUSHU UNIVERSITY, Graduate School of Medical Sciences, Professor (30154917)
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| Project Period (FY) |
2004 – 2006
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| Keywords | PROTEINS / THROMBOSIS / HORMONE REPLACEMENT THERAPY / ESTROGEN |
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| Research Abstract |
1. Investigation of regulatory mechanism of the protein S gene by sex hormone
The effect of various sex hormones on promoter activity of the human protein S gene was examined using plasmid constructs carrying the promoter region of the human protein S gene and luciferase gene in cultured human hepatoma cells. Estrogen suppressed the transcriptional activity of the human protein S gene. Twelve base pairs region in the promoter of the human protein S gene was involved in the inhibitory effect of estrogen on protein S gene transcription.
2. Development of protein S measurement and investigation of regulatory mechanism of protein S in mice
An assay system of mouse protein S was developed by modification of human protein S measurement method. Using this system, we investigated the effects of sex hormones on the protein S level in mice. The plasma level of protein S decreased by treatment of estrogen and human gonadotropin as well as by pregnancy.
3. Association study of protein S polymorphism with the plasma protein S level in Japanese women
We examined the plasma free protein S level in a general Japanese population, and investigated the association of single nucleotide polymorphisms (SNPs) of the protein S gene (PROS1) with the plasma protein S level. Three of 379 Japanese women aged 50-75 years showed reduced plasma free protein S. One of these three had a heterozygous missense mutation (R275C) in the PROS1 gene. Furthermore, 11 individuals were heterozygous carriers with a K155E mutation. We conclude that the estimated prevalence of inherited protein S deficiency in Japanese women is at least 3.2% (12/379). Association analyses showed that a promoter SNP in the PROS1 gene was significantly associated with the free protein S level.
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[Journal Article] Impaired nuclear translocation, nuclear matrix targeting, and intranuclear mobility of mutant androgen receptors carrying amino acid substitutions in the deoxyribonucleic acid-binding domain derived from androgen insensitivity syndrome patients2005
Author(s)
Kawate H, Wu Y, Ohnaka K, Tao R-H, Nakamura K, Okabe T, Yanase T, Nawata H, Takayanagi R
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Journal Title
J Clin Endocrinol Metab 90(11)
Pages: 6162-6169
Description
「研究成果報告書概要(欧文)」より
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