Analysis for crosstalk between estrogen and Wnt signalings

雌激素和 Wnt 信号之间的串扰分析

• 批准号: 23701070
• 负责人: MIYAGAWA Shinichi
• 金额: $ 2.83万
• 依托单位: 大学共同利用機関法人自然科学研究機構(岡崎共通研究施設) (2012)National Institutes of Natural Sciences Okazaki Research Facilities (2011)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23701070/
• 关键词: 女性ホルモン; Wnt; 女性生殖器官; 女性生殖器

An integrated network of endocrine chemicals (hormones) modulates the reproductive systems in most animals. Estrogens, one class of these endocrine hormones, are responsible for the induction of behavioral and physiological processes involving many organ systems. The female reproductive tract provides the sites for gamete fertilization, implantation and subsequent development of the embryo and delivery of the fetus. Organs in the female reproductive tract are also involved in women’s health issues including and tumorigenesis. Growth factors and ER signaling cooperate to play essential roles in cell proliferation, differentiation and tumor progression in mouse reproductive organs. Treatment of neonatal mice with diethylstilbestrol (DES) induces an estrogen-independent persistent proliferation and cornification of the vaginal epithelium, which typically results in cancerous lesions later in life. However, the mechanisms of the estrogen-dependent and -independent pathways had remained essentially unknown. We found that Wnt/beta-catenin signaling is involved in estrogen-independent phenomena in mouse vagina developmentally exposed to estrogens.。

内分泌化学物质（激素）的综合网络调节大多数动物的生殖系统。雌激素是这些内分泌激素中的一类，负责诱导涉及许多器官系统的行为和生理过程。女性生殖道为配子受精、植入和随后的胚胎发育以及胎儿分娩提供场所。女性生殖道中的器官也涉及妇女的健康问题，包括肿瘤的发生。生长因子和ER信号在小鼠生殖器官的细胞增殖、分化和肿瘤进展中发挥重要作用。用己烯雌酚（DES）处理新生小鼠会诱导阴道上皮的雌激素非依赖性持续增殖和角化，这通常会导致生命后期的癌性病变。然而，雌激素依赖性和非依赖性途径的机制基本上仍然未知。我们发现Wnt/β-catenin信号通路参与了小鼠阴道发育暴露于雌激素的雌激素非依赖性现象。

项目成果

Wnt family genes and their modulation in the ovary-independent and persistent vaginal epithelial cell proliferation and keratinization induced by neonatal diethylstilbestrol exposure in mice.

• DOI: 10.1016/j.tox.2012.02.010
• 发表时间: 2012-06
• 期刊: Toxicology
• 影响因子: 4.5
• 作者: Takeshi Nakamura;S. Miyagawa;Y. Katsu;Hajime Watanabe;Takeshi Mizutani;Tomomi Sato;K. Morohashi;T. Takeuchi;T. Iguchi;Y. Ohta

Sequential changes in the expression of Wnt- and Notch-related genes in the vagina and uterus of ovariectomized mice after estrogen exposure

雌激素暴露后去卵巢小鼠阴道和子宫中 Wnt 和 Notch 相关基因表达的连续变化

• 发表时间: 2012
• 期刊: In Vivo
• 影响因子: 2.3
• 作者: Nakamura T;Miyagawa S;Katsu Y;Sato T;Iguchi T;Ohta Y
• 通讯作者: Ohta Y

Indispensable roles of estrogen receptor a for persistent vaginal change induced by neonatal 5a-dihydrotestosterone exposure

雌激素受体 a 对于新生儿 5a-二氢睾酮暴露引起的持续阴道变化起着不可或缺的作用

• 发表时间: 2012
• 作者: Miyagawa S.;Ohta Y.;Iguchi T
• 通讯作者: Iguchi T

Molecular mechanisms of induction of persistent changes by estrogenic chemicals on female reproductive tracts and external genitalia.

雌激素化学物质对女性生殖道和外生殖器诱导持续变化的分子机制。

• 发表时间: 2011
• 期刊: J Steroid Biochem Mol Biol in press
• 作者: Miyagawa S;Sato M;Iguchi T.
• 通讯作者: Iguchi T.

P21 and Notch signalings in the persistently altered vagina induced by neonatal diethylstilbestrol exposure in mice

新生小鼠己烯雌酚暴露导致阴道持续改变的 P21 和 Notch 信号传导

• 发表时间: 2012
• 期刊: J Vet Med Sci
• 影响因子: 1.2
• 作者: Nakamura T;Miyagawa S;Katsu Y;Mizutani T;Sato T;Takeuchi T;Iguchi T;Ohta Y
• 通讯作者: Ohta Y