Endocrine Disrupter Bisphenol A Increases In Situ Estrogen Production in the Mouse Urogenital Sinus

被引：69

作者：

Arase, Shigeki ^{[1
]}

Ishii, Kenichiro ^{[1
]}

Igarashi, Katsuhide ^{[2
]}

Aisaki, Kenichi ^{[2
]}

Yoshio, Yuko ^{[1
]}

Matsushima, Ayami ^{[3
]}

Shimohigashi, Yasuyuki ^{[3
]}

Arima, Kiminobu ^{[1
]}

Kanno, Jun ^{[2
]}

Sugimura, Yoshiki ^{[1
]}

机构：

[1] Mie Univ, Grad Sch Med, Dept Nephrourol Surg & Androl, Tsu, Mie 5148507, Japan

[2] Natl Inst Hlth Sci, Div Cellular & Mol Toxicol, Tokyo, Japan

[3] Kyushu Univ, Fac Sci, Dept Chem, Lab Struct Funct Biochem, Fukuoka 812, Japan

来源：

BIOLOGY OF REPRODUCTION | 2011年 / 84卷 / 04期

关键词：

aromatase; bisphenol A; developmental biology; embryo; estradiol/estrogen receptor; in situ estrogen production; male reproductive tract; prostate; steroidogenic enzyme; urogenital sinus; GENE-EXPRESSION; INSTRUCTIVE INDUCTION; PROSTATIC DEVELOPMENT; UTERO EXPOSURE; RECEPTOR-GAMMA; MAMMARY-GLAND; HUMAN HEALTH; ERR-GAMMA; DIFFERENTIATION; GROWTH;

D O I：

10.1095/biolreprod.110.087502

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The balance between androgens and estrogens is very important in the development of the prostate, and even small changes in estrogen levels, including those of estrogen-mimicking chemicals, can lead to serious changes. Bisphenol A (BPA), an endocrine-disrupting chemical, is a well-known, ubiquitous, estrogenic chemical. To investigate the effects of fetal exposure to low-dose BPA on the development of the prostate, we examined alterations of the in situ sex steroid hormonal environment in the mouse urogenital sinus (UGS). In the BPA-treated UGS, estradiol (E-2) levels and CYP19A1 (cytochrome P450 aromatase) activity were significantly increased compared with those of the untreated and diethylstilbestrol (DES)-treated UGS. The mRNAs of steroidogenic enzymes, Cyp19a1 and Cyp11a1, and the sex-determining gene, Nr5a1, were up-regulated specifically in the BPA-treated group. The up-regulation of mRNAs was observed in the mesenchymal component of the UGS as well as in the cerebellum, heart, kidney, and ovary but not in the testis. The number of aromatase-expressing mesenchymal cells in the BPA-treated UGS was approximately twice that in the untreated and DES-treated UGS. The up-regulation of Esrrg mRNA was observed in organs for which mRNAs of steroidogenic enzymes were also up-regulated. We demonstrate here that fetal exposure to low-dose BPA has the unique action of increasing in situ E-2 levels and CYP19A1 (aromatase) activity in the mouse UGS. Our data suggest that BPA might interact with in situ steroidogenesis by altering tissue components, such as the accumulation of aromatase-expressing mesenchymal cells, in particular organs.

引用

页码：734 / 742

页数：9