• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2007 Fiscal Year Final Research Report Summary

A possible mechanism for decrease in serum thyroxine level by polychlorinated biphenyls

Research Project

Project/Area Number 18510061
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Risk sciences of radiation/Chemicals
Research InstitutionTokushima Bunri University

Principal Investigator

KATO Yoshihisa  Tokushima Bunri University, Kagawa School of Pharmaceutical Sciences, Associate Professor (90161132)

Project Period (FY) 2006 – 2007
Keywordspolychlorinated biphenyl / endocrine-disrupter / thyroxine / UDP-glucuronosyltransferase / human / liver / tranthyretin / Kanechlor-500
Research Abstract

In the present study, we determined whether or not a consecutive treatment with Kanechlor-500 (KC500) at a relatively low dose (10 mg/kg, i.p., once daily for 10 days) results in decrease in the level of serum total thyroxine (T_4) and further investigated an exact mechanism for the KC500-induced decrease in the T_4. At 4 days after final treatment with KC500, the serum total T_4 and free T_4 levels were markedly decreased in both Wistar and UGT1A-deficient Wistar (Gunn) rats, while significant increases in hepatic T_4-UDP-glucuronosyltransferase (T_4-UDP-GT) activity were observed in Wistar rats but not in Gunn rats. Level of serum thyroid-stimulating hormone was not significantly changed in either Wistar or Gunn rats. Clearance from serum of the [^<125>I]T_4 administered to the KC500-pretreated Wistar and Gunn rats was faster than that to the corresponding control (KC500-untreated) rats. The accumulated level of [^<125>I]T_4 was increased in several tissues, especially the liver, in … More the KC500-pretreated rats. The present findings demonstrated that a consecutive treatment with KC500 resulted in significant decrease in level of serum total T_4 in both Wistar and Gunn rats and further indicated that the KC500-induced decrease would occur through increase in accumulation of T_4 in several tissues, especially the liver, rather than increase in hepatic T_4-UDP-GT activity.
To clarify the UGT isoform(s) responsible for the glucuronidation of thyroid hormone T_4 in the human liver, the T_4-glucuronidation activities of recombinant human UGT isoforms and 7 individual human liver microsomes were comparatively examined. The findings strongly indicated that glucuronidation of T_4 in the human liver was mediated by UGT1A subfamily enzymes, especially UGT1A1 and UGT1A3, and further suggested that the interindividual difference would come from that in the expression levels of UGT1A1 and UGT1A3 in individual human livers. Further studies are necessary for understanding the susceptibility toward a PCB-mediated decrease in serum T_4 level in animals including humans. Less

  • Research Products

    (34 results)

All 2008 2007 2006 Other

All Journal Article (18 results) (of which Peer Reviewed: 8 results) Presentation (15 results) Remarks (1 results)

  • [Journal Article] Hepatic UDP-glucuronosyltransferases responsible for glucuronidation of thyroxine in humans2008

    • Author(s)
      Yoshihisa Kato
    • Journal Title

      Drug Metab.Dispos. 36

      Pages: 51-55

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Hepatic UDP-glucuronosyltransferases responsible for glucuronidation of thyroxine in humans.2008

    • Author(s)
      Yoshihisa Kato
    • Journal Title

      Drug Metab. Dispos. 36

      Pages: 51-55

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A novel mechanism for polychlorinated biphenyl-induced decrease in serum thyroxine level in rats2007

    • Author(s)
      Yoshihisa Kato
    • Journal Title

      Drug Metab.Dispos. 35

      Pages: 1949-1955

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Thyroxine-metabolizing rat uridine diphosphate-glucuronosyltransferase 1A7 is regulated by thyroid hormone receptor2007

    • Author(s)
      Yoshikazu Emi
    • Journal Title

      Endocrinology 148

      Pages: 6124-6133

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] 2,2',4,5,5'-五塩素化ビフェニル(CB101)のラット,ハムスターおよびモルモット肝ミクロゾームによる代謝2007

    • Author(s)
      太田 千穂
    • Journal Title

      福岡医学雑誌 98

      Pages: 236-244

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The formation of a catechol metabolite of 2,2',4,5,5'-pentachlorobiphenyl(CB101)by liver microsomes from rats,hamsters,guinea pigs and humans2007

    • Author(s)
      Nobuyuki Koga
    • Journal Title

      Organohalogen Compounds 69

      Pages: 1757-1760

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] The distribution of metabolites of 2,2',3,4,4',5',6-heptachlorobiphenyl(CB183)in rats and guinea pigs2007

    • Author(s)
      Chiho Ohta
    • Journal Title

      Organohalogen Compounds 69

      Pages: 1761-1764

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] A novel mechanism for polychlorinated biphenyl-induced decrease in serum thyroxine level in rats.2007

    • Author(s)
      Yoshihisa Kato
    • Journal Title

      Drug Metab. Dispos. 35

      Pages: 1949-1955

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Thyroxine-metabolizing rat uridine diphosphate-glucuronosyltransferase 1A7 is regulated by thyroid hormone receptor.2007

    • Author(s)
      Yoshikazu Emi
    • Journal Title

      Endocrinology 148

      Pages: 6124-6133

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Metabolism of 2, 2', 4, 5, 5', 5-pentachlorobiphenyl(CB101) by liver microsomes of rats, hamsters and guinea pig.2007

    • Author(s)
      Chiho Ohta
    • Journal Title

      Fukuoka Acta Medica 98

      Pages: 236-244

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The formation of a catechol metabolite of 2, 2', 4, 5, 5'-pentachlorobiphenyl(CB101) by liver microsomes from rats, hamsters, guinea pigs and humans.2007

    • Author(s)
      Nobuyuki Koga
    • Journal Title

      Organohalogen Compd. 69

      Pages: 1757-1760

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The distribution of metabolites of 2, 2', 3, 4, 4', 5', 6-heptachlorobiphenyl(CB183) in rats and guinea pigs.2007

    • Author(s)
      Chiho Ohta
    • Journal Title

      Organohalogen Compd. 69

      Pages: 1761-1764

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Monospecific antipeptide antibodies against human hepatic UDP-glucuronosyl-transferase 1A subfamily(UGT1A)isoforms2006

    • Author(s)
      Shin-ichi Ikushiro
    • Journal Title

      Drug Metab.Pharmacokinet 21

      Pages: 70-74

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] A possible mechanism for the decrease in serum thyroxine level by polychlorinated biphenyls in Wistar and Gunn rats2006

    • Author(s)
      Yoshihisa Kato
    • Journal Title

      Organohalogen Compounds 68

      Pages: 1442-1445

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] In vitro metabolism of 2,2',3,4,4',5',6-heptachlorobiphenyl(CB183)with liver microsomes from rats,guinea pigs and hamsters2006

    • Author(s)
      Chiho Ohta
    • Journal Title

      Organohalogen Compounds 68

      Pages: 1733-1736

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Monospecific antipeptide antibodies against human hepatic UDP-glucuronosyltransferase lA subfamily(UGT1A) isoforms.2006

    • Author(s)
      Shin-ichi Ikushiro
    • Journal Title

      Drug Metab. Pharmacokinet. 21

      Pages: 70-74

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A possible mechanism for the decrease in serum thyroxine level by polychlorinated biphenyls in Wistar and Gunn rats.2006

    • Author(s)
      Yoshihisa Kato
    • Journal Title

      Organohalonen Compd. 68

      Pages: 1442-1445

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] In vitro metabolism of 2, 2', 3, 4, 4', 5', 6-heptachlorobiphenyl(CB183) with liver microsomes from rats, guinea pigs and hamsters.2006

    • Author(s)
      Chiho Ohta
    • Journal Title

      Organohalonen Compd. 68

      Pages: 1733-1736

    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] 2,2',4,5,5'-五塩素化ビフェニル(PCB101)のラット,ハムスター,モルモットおよびヒト肝ミクロゾームによる代謝2008

    • Author(s)
      太田 千穂
    • Organizer
      第128年会日本薬学会, 講演要旨集3(p.181)
    • Place of Presentation
      横浜
    • Year and Date
      2008-03-27
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] 母乳中に残留する天然有機ハロゲン化合物の環境起源調査2008

    • Author(s)
      原口 浩一
    • Organizer
      第128年会日本薬学会, 講演要旨集3(p.175)
    • Place of Presentation
      横浜
    • Year and Date
      2008-03-27
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] 2,2',3,4',5,5'-六塩素化ビフェニル(PCB146)の動物肝ミクロゾームによる代謝2007

    • Author(s)
      太田 千穂
    • Organizer
      フォーラム2007:衛生薬学・環境トキシコロジー, 講演要旨集(P.198)
    • Place of Presentation
      大阪
    • Year and Date
      2007-11-02
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Species differences in the metabolism of 2, 2', 3, 4', 5, 5'-hexachlorobiphenyl(PCB 146) by liver microsomes of rats, guinea pigs and hamsters.2007

    • Author(s)
      Chiho Ohta
    • Organizer
      Forum2007 : Pharmaceutical Health Science-Environmental Toxicology
    • Place of Presentation
      (Osaka), J. Health Sci
    • Year and Date
      2007-11-02
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] PCBによる血中サイロキシン濃度低下機構の解明2007

    • Author(s)
      玉置 尺尋
    • Organizer
      第127年会日本薬学会, 講演要旨集3(p.153)
    • Place of Presentation
      富山
    • Year and Date
      2007-03-29
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] 七塩素化ビフェニルのヒト肝におけるin vitro代謝2007

    • Author(s)
      太田 千穂
    • Organizer
      第127年会日本薬学会, 講演要旨集2(p.181)
    • Place of Presentation
      富山
    • Year and Date
      2007-03-28
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Development of isoform-specific antipeptide antibodies against human UDP-glucuronosyltransferase 1A subfamily(UGT1A)2006

    • Author(s)
      Shin-ichi Ikushiro
    • Organizer
      21st JSSX Annual Meeting, Abstract(p.353)
    • Place of Presentation
      Tokyo
    • Year and Date
      2006-11-30
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Development of isoform-specific antipeptide antibodies against human UDP-glucuronosyltransferase 1A subfamily (UGTIA).2006

    • Author(s)
      Shin-ichi Ikushiro
    • Organizer
      21st JSSX Annual Meeting
    • Place of Presentation
      (Tokyo), Abstract
    • Year and Date
      2006-11-30
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] 2,2',4,5,5',6-七塩素化ビフェニル(PCB183)のラットにおけるin vivo代謝2006

    • Author(s)
      太田 千穂
    • Organizer
      フォーラム2006:衛生薬学・環境トキシコロジー, 講演要旨集(P.143)
    • Place of Presentation
      東京
    • Year and Date
      2006-10-30
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] In vivo metabolism of 2, 2', 3, 4, 4', 5', 6-heptachlorobiphenyl(PCB183) in rats.2006

    • Author(s)
      Chiho Ohta
    • Organizer
      Forum2006 : Pharmaceutical Health Science-Environmental Toxicology
    • Place of Presentation
      (Tokyo), Abstract
    • Year and Date
      2006-10-30
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] 2,2',4,5,5'-五塩素化ビフェニル(PCB101)のin vitro代謝2006

    • Author(s)
      尾崎 真理
    • Organizer
      第92回日本食品衛生学会学術講演会, 講演要旨集(p.52)
    • Place of Presentation
      愛知
    • Year and Date
      2006-10-27
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] 高残留性七塩素化ビフェニル4-水酸化体の生成メカニズム2006

    • Author(s)
      太田 千穂
    • Organizer
      第92回日本食品衛生学会学術講演会, 講演要旨集(p.53)
    • Place of Presentation
      愛知
    • Year and Date
      2006-10-27
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] 4-OH-2,2',3,4',5,5',6-heptachlorobiphenylの血中甲状腺ホルモン濃度におよぼす影響2006

    • Author(s)
      加藤 善久
    • Organizer
      第33回日本トキシコロジー学会学術年会, J.Toxicol.Sci., (31Supple.), S221
    • Place of Presentation
      名古屋
    • Year and Date
      2006-07-05
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Reduction of thyroid hormone level by 4-OH-2, 2', 3, 4', 5, 5', 6-heptachlorobiphenyl in mice.2006

    • Author(s)
      Sekihiro Tamaki
    • Organizer
      The 33rd Annual Meeting of the Japanese Society of Toxicology
    • Place of Presentation
      (Nagoya), J. Toxicol. Sci
    • Year and Date
      2006-07-05
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] 2,2',3,4,4',5',6-七塩素化ビフェニル(PCB183)のin vivo代謝の動物種差2006

    • Author(s)
      太田 千穂
    • Organizer
      第126年会日本薬学会, 講演要旨集3(p.179)
    • Place of Presentation
      仙台
    • Year and Date
      2006-03-29
    • Description
      「研究成果報告書概要(和文)」より
  • [Remarks] 「研究成果報告書概要(和文)」より

    • URL

      http://kp.bunri-u.ac.jp/kph17/index.html

URL: 

Published: 2010-02-04  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi