Basic and clinical research of insulin resistance in reproductive-endocrine region

生殖内分泌区胰岛素抵抗的基础与临床研究

• 批准号: 17591719
• 负责人: TAKEUCHI Toru
• 金额: $ 2.37万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17591719/
• 关键词: Reproduction; Endocrinology; Ovarian function; Obesity; Insulin; Polycystic ovary syndrome; Endocrine disruptor; Bisphenol A; 多嚢胞性卵巣症候群; 内分泌撹乱物質; 内分泌撹乱化学物質

Insulin resistance is closely related to obesity, abnormal glucose tolerance, hypertension and hyperlipidemia, and is also thought to be the cause of Metabolic Syndrome. In the region of reproductive endocrinology, the close relation between insulin resistance and the clinical condition of polycystic ovary syndrome is suggested. The purpose of this study is to investigate gynecological disease states with insulin resistance using epidemiological, biochemical, physiological, and molecular biological methods. Also, we reported for the first time that endocrine disruptor, bisphenol A, is significantly higher in blood in women with polycystic ovary syndrome and obese women. Therefore, we also investigated the relation between insulin resistance and endocrine disruptor, bisphenol A (BPA).Insulin resistance is generally recognized in obese women, but was recognized even in both obese and non-obese women with polycystic ovary syndrome. We found out that the area under the curve (AUC) for insulin is a better index than Homeostasis Model Assessment-insulin resistance (HOMA-IR) to diagnose insulin resistance in women with polycystic ovary syndrome. Additionally, we found out that the cause of susceptibility for growth hormone secretion to be suppressed in PCOS patients with insulin resistance was hyperandrogenemia.Analysis of the mRNA expression of UDP-glucuronosyltransferase 2B1 (UGT2B1) by real-time quantitative RTPCR revealed that the relative expression level of UGT2B1 mRNA showed a testosterone propionate (TP) dose-dependent decrease. The results of enzyme analyses demonstrated that the ratio of BPA glucuronidation and the expression level of UGT2B1 mRNA were significantly lower under the hyperandrogenemic conditions. The clearance of BPA may be slowed in a TP dose-dependent manner, resulting in an increase of serum BPA concentration under hyperandrogenemic conditions such as PCOS patients.

胰岛素抵抗与肥胖、糖耐量异常、高血压和高脂血症密切相关，也被认为是代谢综合征的病因。在生殖内分泌学领域，胰岛素抵抗与多囊卵巢综合征的临床状况密切相关。本研究旨在通过流行病学、生物化学、生理学和分子生物学方法，探讨胰岛素抵抗的妇科疾病状态。此外，我们首次报道了内分泌干扰物双酚A在多囊卵巢综合征和肥胖女性血液中的含量明显较高。因此，我们也研究了胰岛素抵抗与内分泌干扰物双酚A（BPA）的关系。胰岛素抵抗通常在肥胖女性中被认识到，但即使在肥胖和非肥胖的多囊卵巢综合征女性中也被认识到。我们发现胰岛素曲线下面积（AUC）是一个比稳态模型评估-胰岛素抵抗（HOMA-IR）更好的诊断多囊卵巢综合征患者胰岛素抵抗的指标。实时荧光定量RT-PCR检测UGT-葡萄糖醛酸转移酶2B 1（UGT 2B 1）mRNA表达水平，发现UGT 2B 1 mRNA的相对表达水平呈丙酸睾酮（TP）剂量依赖性降低。酶分析结果表明，在高雄激素血症条件下，BPA葡萄糖醛酸化的比率和UGT 2B 1 mRNA的表达水平显着降低。BPA的清除可能以TP剂量依赖性方式减慢，导致高雄激素血症条件下（如PCOS患者）血清BPA浓度升高。

项目成果

生殖内分泌・不妊、「無排卵周期症」

生殖内分泌/不孕症，“无排卵周期障碍”

• 发表时间: 2008
• 期刊: 産科と婦人科 75
• 作者: Takeuchi T;et. al.;竹内 亨
• 通讯作者: 竹内 亨

Elevated serum bisphenol A levels under hyperandrogenic conditions may be caused by decreased UDP-glucuronosyltransferase activity

• DOI: 10.1507/endocrj.k06-032
• 发表时间: 2006-08-01
• 期刊: ENDOCRINE JOURNAL
• 影响因子: 2
• 作者: Takeuchi, Toru;Tsutsumi, Osamu;Taketani, Yuji
• 通讯作者: Taketani, Yuji

Sexual cycle and leptin

性周期和瘦素

• 发表时间: 2006
• 期刊: Hormone Frontier in Gynecology 13
• 作者: Takeuchi T;Tsutsumi O;et. al.;Takeuchi T
• 通讯作者: Takeuchi T

内分泌【頻発月経・希発月経】

内分泌【月经频数/月经稀发】

• 发表时间: 2007
• 期刊: 臨床婦人科産科 61
• 作者: Minaguchi T;Nakagawa S;Takazawa Y;Nei T;Horie K;Fujiwara T;Osuga Y;Yasugi T;Kugu K;Yano T;Yoshikawa H;Taketani Y.;竹内 亨
• 通讯作者: 竹内 亨

内分泌【頻発月経・希発月経】.

内分泌学[月经频繁/月经稀发]。

• 发表时间: 2007
• 期刊: 臨床婦人科産科 61
• 作者: Kikuchi A;Kozuma S;Yasugi T;Taketani Y.;竹内 亨
• 通讯作者: 竹内 亨