Bisphenol A may cause testosterone reduction by adversely affecting both testis and pituitary systems similar to estradiol
Bisphenol A may cause testosterone reduction by adversely affecting both testis and pituitary systems similar to estradiol
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DOI：
10.1016/j.toxlet.2010.02.002
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发表时间：
2010-04-15
影响因子：
3.5
通讯作者：
Nakajima, Tamie
中科院分区：
文献类型：
--
作者：
Nakamura, Daichi;Yanagiba, Yukie;Nakajima, Tamie
双酚A（BPA）引起生殖毒性，但其机制尚不清楚。在本研究中，我们试图澄清这些机制相比，17 β-雌二醇（E2）。对青春期前Wistar/ST雄性大鼠（4周龄）皮下注射BPA（0、20、100和200 mg/kg/天）或E2（10和100 μ g/kg/天）6周。BPA和E2治疗降低血浆和睾丸睾酮水平，血浆促黄体生成素（LH），但不E2和卵泡刺激素水平，虽然E2治疗增加其血浆水平。与睾酮水平下降有关，BPA和E2降低了Leydig细胞中类固醇生成酶和胆固醇载体蛋白的表达。因此，血浆中睾酮水平降低可能是由于这些酶和蛋白质的表达降低以及血浆LH水平降低所致。有趣的是，类固醇生成酶和载体蛋白的变化在BPA或E2暴露水平低于抑制血浆LH水平时观察到。显微镜下，200毫克/公斤BPA和100微克/公斤E2显着减少睾丸间质细胞的数量。BPA和E_2还可降低大鼠睾丸间质细胞雌激素受体α-mRNA的表达，这可能与睾丸间质细胞数量减少有关。因此，BPA不仅直接影响Leydig细胞，而且还影响脑垂体，但前者在较低的暴露浓度下可能比后者受损。(C)2010爱思唯尔爱尔兰有限公司版权所有。
Bisphenol A (BPA) causes reproductive toxicities, but the mechanisms are still unclear. In the present study, we sought to clarify these mechanisms in comparison with those of 17 beta-estradiol (E2). Prepubertal Wistar/ST male rats (4 weeks old) were subcutaneously administered BPA (0, 20, 100 and 200 mg/kg/day) or E2 (10 and 100 mu g/kg/clay) for 6 weeks. Both BPA and E2 treatments decreased plasma and testicular testosterone levels, and plasma luteinizing hormone (LH), but not E2 and follicle-stimulating hormone levels, though E2 treatment increased its plasma level. In relation to the decreased testosterone levels, BPA and E2 decreased expressions of steroidogenic enzymes and cholesterol carrier protein in Leydig cells. Thus, decreased testosterone levels in plasma might have resulted from decreased expressions of these enzymes and protein as well as from decreased plasma LH levels. Interestingly, the changes in steroidogenic enzymes and carrier protein were observed at lower levels of exposure to BPA or E2 than those inhibiting plasma LH levels. Microscopically, 200 mg/kg BPA and 100 mu g/kg E2 significantly decreased Leydig cell numbers in the testis. In addition, BPA and E2 also decreased expression of estrogen receptor a-mRNA, which might be related to the decreased numbers of Leydig cells. Thus, BPA directly affects not only the Leydig cells but also the pituitary gland, but the former may be impaired at lower exposure concentrations than the latter. (C) 2010 Elsevier Ireland Ltd. All rights reserved.