研究者詳細 - 増山　寿

MISC - 増山　寿

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Endocrine disrupting chemicals, phthalic acid and nonylphenol, activate Pregnane X receptor-mediated transcription

Hisashi Masuyama, Yuji Hiramatsu, Mamoru Kunitomi, Takafumi Kudo, Paul N. MacDonald

Molecular Endocrinology 14 ( 3 ) 421 - 428 2000年

記述言語：英語出版者・発行元：Endocrine Society

Recently, Pregnane X receptor (PXR), a new member of the nuclear receptor superfamily, was shown to mediate the effects of several steroid hormones, such as progesterone, glucocorticoid, pregnenolone, and xenobiotics on cytochrome P450 3A genes (CYP3A) through the specific DNA sequence for CYP3A, suggesting that PXR may play a role in steroid hormone metabolism. In this paper, we demonstrated that phthalic acid and nonylphenol, endocrine-disrupting chemicals (EDCs), stimulated PXR-mediated transcription at concentrations comparable to those at which they activate estrogen receptor-mediated transcription using a transient reporter gene expression assay in COS-7 cells. However, bisphenol A, another EDC, had no effect on PXR-mediated transcription, although this chemical significantly enhanced ER-mediated transcription. In the yeast two-hybrid protein interaction assay, PXR interacted with two nuclear receptor coactivator proteins, steroid hormone receptor coactivator-1 and receptor interacting protein 140, in the presence of phthalic acid or nonylphenol. Thus, EDC-occupied PXR may regulate its specific gene expression through the receptor-coactivator interaction. In contrast, these EDCs had no effect on the interaction between PXR and suppressor for gal 1, a component of proteasome. Finally, the expression of CYP3A1 mRNA in the liver of rats exposed to phthalic acid or nonylphenol markedly increased compared with that in rats treated with estradiol, bisphenol A, or ethanol as assessed by competitive RT-PCR. These data suggest that EDCs may affect endocrine functions by altering steroid hormone metabolism through PXR.

DOI： 10.1210/mend.14.3.0424

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Endocrine Disrupting Chemicals Phthalic Acid and Nonylphenol Activate Pregnane X Receptor-mediated Transcription (共著)

Molecular Endocrinology 14 ( 3 ) 421 - 428 2000年

Streptozotocin-induced diabetic pregnant rats exhibit signs and symptoms mimicking preeclampsia

Go Ishihara, Yuji Hiramatsu, Hisashi Masuyama, Takafumi Kudo

Metabolism: Clinical and Experimental 49 ( 7 ) 853 - 857 2000年

記述言語：英語出版者・発行元：W.B. Saunders

The number of patients with hypertension, obesity, diabetes, and hyperlipidemia is increasing. This tendency is observed in pregnant women, in whom many obstetrical and perinatal complications occur. The prevention of these abnormalities is important in reducing perinatal mortality and the risk of coronary disease. We established a pregnant rat model with diabetes and signs and symptoms mimicking preeclampsia. On day 6 of pregnancy, streptozotocin (STZ) or citrate buffer was injected into the tail vein. After STZ administration, plasma glucose was increased within 48 hours and sustained at a high level until day 20 of pregnancy, and plasma insulin was decreased. Fetuses from STZ-treated mothers were growth-restricted, and plasma glucose was 6-fold higher in fetuses of STZ-treated versus control rats. The systolic blood pressure, urinary protein, and hematocrit were increased significantly in STZ-treated rats. Total cholesterol and triglycerides were also elevated in STZ-treated rats, but plasma leptin levels were decreased. The STZ-induced diabetic pregnant rat model exhibited preeclampsia, hemoconcentration, hyperlipidemia, hypoleptinemia, and intrauterine growth restriction. This model closely mimics the features of human pregnancy complicated by diabetes and is useful for the basic study of the pathophysiology of pregnancy with diabetes. Copyright (C) 2000 by W.B. Saunders Company.

DOI： 10.1053/meta.2000.6750

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★101 内分泌攪乱物質のPregnane X Receptorを介したステロイド代謝に及ぼす影響

増山寿, 井下秀司, 国富衛, 水谷靖司, 平松祐司, 工藤尚文

日本産科婦人科學會雜誌 52 ( 2 ) "260(S - 184)" 2000年

P-495 肥満妊婦における妊娠糖尿病スクリーニングはいかに行うべきか?

深井佳恵, 平松祐司, 大橋美佐保, 熊澤一真, 中田高公, 増山寿, 水谷靖司, 工藤尚文, 小国信嗣, 小国美種, 大本裕之, 吉田信隆

日本産科婦人科學會雜誌 52 ( 2 ) "537(S - 461)" 2000年

P-262 収縮能および拡張能を連合させた超音波ドプラ指標による心機能評価法であるTei indexの胎児における正常値と各種病態における有用性

多田克彦, 中田高公, 大橋美佐保, 橋本一真, 熊澤一真, 増山寿, 中塚幹也, 工藤尚文

日本産科婦人科學會雜誌 52 ( 2 ) "460(S - 384)" 2000年

超低出生体重児のwell-beingの評価法一胎児心拍数図および胎児血流計測値と分娩時臍帯動脈血ガス分析値との関係一

多田克彦, 工藤尚文, 中田高公, 橋本一郎, 熊澤一真, 増山寿, 中塚幹也

産婦人科の世界 2000年

本態性血小板血症合併妊娠の1症例

舛本明生, 増山寿, 橋本一郎, 熊澤一真, 高田雅代, 中田高公, 中塚幹也, 水谷靖司, 多田克彦, 平松祐司, 工藤尚文

日本産科婦人科学会中国四国合同地方部会雑誌 2000年

妊娠26週で胎内診断した左心低形成症候群における胎児大血管径の推移

多田克彦, 山田聡, 熊澤一真, 高田雅代, 中田高公, 増山寿, 中塚幹也, 工藤尚文, 大月審一

Journal of medical ultrasonics = 超音波医学 26 ( 12 ) 1211 - 1216 1999年12月

排卵、妊娠、産褥期におけるビタミンD代謝について

上村茂仁, 田淵和久, 伊藤裕徳, 増山寿, 水谷靖司, 中塚幹也, 平松祐司, 工藤尚文

日本骨代謝学会雑誌 = Japanese journal of bone metabolism 17 ( 2 ) 280 - 280 1999年6月

産婦人科手術におけるバイポーラシザースの応用

水谷靖司, 平松祐司, 増山寿, 上村茂仁, 児玉順一, 小橋勇二, 奥田博之, 工藤尚文

産婦人科手術 10: 117-123 1999年

312 新しい核内レセプター, Pregnane X receptor (PXR)の解析とその発現

増山寿, 国富衛, 上村茂仁, 水谷靖司, 平松祐司, 工藤尚文

日本産科婦人科學會雜誌 51 "S - 290" 1999年

P-207 妊娠糖尿病のスクリーニング法に関する検討 : どのような妊婦に必ずスクリーニングすべきか

大橋美佐保, 平松祐司, 石原剛, 増山寿, 水谷靖司, 上村茂仁, 工藤尚文, 小国信嗣, 小国美種, 松岡巌, 関正明, 今井香里

日本産科婦人科學會雜誌 51 "S - 463" 1999年

P-175 排卵,妊娠,産褥期におけるビタミンD代謝機構について.

上村茂仁, 平松祐司, 国富衛, 伊藤裕徳, 増山寿, 水谷靖司, 中塚幹也, 工藤尚文

日本産科婦人科學會雜誌 51 "S - 447" 1999年

P-439 周術期の凝固線溶能からみた術後血栓症予防に対するヘパリンの至適投与法について

水谷靖司, 小橋勇二, 児玉順一, 楠本知行, 増山寿, 上村茂仁, 平松祐司, 奥田博之, 工藤尚文

日本産科婦人科學會雜誌 51 "S - 578" 1999年

Proteasome-mediated degradation of the vitamin D receptor (VDR) and a putative role for SUG1 interaction with the AF-2 domain of VDR

H Masuyama, PN MacDonald

JOURNAL OF CELLULAR BIOCHEMISTRY 71 ( 3 ) 429 - 440 1998年12月

記述言語：英語出版者・発行元：WILEY-LISS

The AF-2 helix of nuclear receptors is essential for ligand-activated transcription, and it may function to couple the receptor to transcriptional coactivator proteins. This domain also contacts components of the proteasome machinery, suggesting that nuclear receptors may be targets for proteasome-mediated proteolysis. In the present study, we demonstrate that mSUG1 (P45), a component of the 26S proteasome, interacts in a 1,25-(OH)(2)D-3-dependent manner with the AF-2 domain of the vitamin D receptor (VDR). Furthermore, treatment of ROS 17/2.8 osteosarcoma cells with the proteasome inhibitors MG132 or beta-lactone increased steady-state levels of the VDR protein. In the presence cycloheximide (10 mu g/ml), the liganded VDR protein was degraded with a half-life of approximately 8 h, and this rate of degradation was completely blocked by 0.05 mM MG132. The role of SUG1-VDR interaction in this process was investigated in transient expression studies. Overexpression of wild-type mSUG1 in ROS17/2.8 cells generated a novel proteolytic VDR fragment of approximately 50 kDa, and its production was blocked by proteasome inhibitors or by a nonhydrolyzable ATP analog. Parallel studies with SUG1 (K196H), a mutant that does not interact with the VDR, did not produce the 50 kDa VDR fragment. Functionally, expression of SUG1 in a VDR-responsive reporter gene assay resulted in a profound inhibition of 1,25-(OH)(2)D-3-activated transcription, while expression of SUG1(K196H) had no significant effect in this system. These data show that the AF-2 domain of VDR interacts with SUG1 ina 1,25-(OH)(2)D-3-dependent fashion and that this interaction may target VDR to proteasome-mediated degradation as a means to downregulate the 1,25-(OH)(2)D-3-activated transcriptional response. J. Cell. Biochem. 71 :429-440, 1998. (C) 1998 Wiley-Liss, Inc.

DOI： 10.1002/(SICI)1097-4644(19981201)71:3<429::AID-JCB11>3.0.CO;2-P

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Proteasome を介した Vitamin D receptor (VDR) 分解と VDR-Suppressor for gal 1 (SUG1) 結合

増山寿, MACDONALD Paul N, 国富衛, 伊藤裕徳, 上村茂仁, 水谷靖司, 平松祐司, 工藤尚文

日本骨代謝学会雑誌 = Japanese journal of bone metabolism 16 ( 2 ) 75 - 75 1998年7月