赖媛艳, 李宏昀, 马晓薇, 江志红, 吴军. 砷暴露对大鼠E2和TRH及其受体mRNA表达的影响[J]. 环境与职业医学, 2023, 40(1): 89-94. DOI: 10.11836/JEOM22274
引用本文: 赖媛艳, 李宏昀, 马晓薇, 江志红, 吴军. 砷暴露对大鼠E2和TRH及其受体mRNA表达的影响[J]. 环境与职业医学, 2023, 40(1): 89-94. DOI: 10.11836/JEOM22274
LAI Yuanyan, LI Hongyun, MA Xiaowei, JIANG Zhihong, WU Jun. Effects of arsenic exposure on E2 and TRH and their receptor mRNA expressions in rats[J]. Journal of Environmental and Occupational Medicine, 2023, 40(1): 89-94. DOI: 10.11836/JEOM22274
Citation: LAI Yuanyan, LI Hongyun, MA Xiaowei, JIANG Zhihong, WU Jun. Effects of arsenic exposure on E2 and TRH and their receptor mRNA expressions in rats[J]. Journal of Environmental and Occupational Medicine, 2023, 40(1): 89-94. DOI: 10.11836/JEOM22274

砷暴露对大鼠E2和TRH及其受体mRNA表达的影响

Effects of arsenic exposure on E2 and TRH and their receptor mRNA expressions in rats

  • 摘要: 背景

    砷能够进入下丘脑诱导雌激素效应并干扰神经内分泌系统正常功能。甲状腺内分泌系统(下丘脑-垂体-甲状腺轴)作为主要的内分泌系统之一,砷对其毒性机制尚不明确。

    目的

    为了解不同砷暴露水平下对大鼠雌二醇(E2)、下丘脑促甲状腺激素释放激素(TRH)及其受体(ERα、ERβ、TRHR)mRNA的影响及其可能的下丘脑毒作用途径与机制。

    方法

    70只Wister大鼠随机分组为:正常对照组(无菌水);低、中、高剂量砷染毒组(0.8、4.0、20.0 mg·kg−1 亚砷酸钠);雌激素受体抑制剂(ICI182780)干预低、中、高剂量砷染毒组;每组10只,雌雄各半。染毒组大鼠给予19周NaAsO2饮水染毒,干预组于第9周经尾静脉注射0.5 mg·kg−1 ICI182780,每周3次。通过ELISA检测大鼠血清中的E2、TRH水平;实时荧光定量PCR(RT-PCR)法检测大鼠下丘脑组织中雌激素受体α(ERα)、雌激素受体β(ERβ)和TRH受体(TRHR) mRNA表达水平。

    结果

    (1) E2及其受体mRNA:与对照组相比,雌性大鼠血清E2水平在低、中剂量砷染毒组上升(P<0.05),雄性大鼠血清E2水平在低、中、高剂量砷染毒组上升(P<0.05),雌性E2变化大于雄性;在下丘脑组织中,与对照组相比,雌性大鼠ERαERβ mRNA相对表达量在低、中、高剂量砷染毒组上升(P<0.05),雄性大鼠ERα mRNA相对表达量在低、中、高剂量砷染毒组上升(P<0.05)。(2)TRH及其受体TRHR mRNA:与对照组相比,雌性大鼠血清TRH水平在高剂量砷染毒组上升(P<0.05),雌性大鼠TRHR mRNA相对表达量在低、中、高剂量砷染毒组上升(P<0.05)。(1)和(2)结果提示雌性较雄性更易出现砷暴露后E2及其受体和TRH及其受体基因的异常改变。(3)与雌性大鼠中高剂量砷染毒组相比,增加ICI182780干预后,抑制了砷暴露诱导TRH、TRHR的表达(P<0.05),提示在下丘脑中砷可能是通过诱发类雌激素效应对TRH、TRHR产生毒作用。

    结论

    砷暴露可以在下丘脑诱发类雌激素效应,干扰甲状腺功能,并表现出剂量依赖及性别差异。E2及TRH及其受体可能是砷类雌激素效应的毒作用途径。

     

    Abstract: Background

    Arsenic can enter the hypothalamus to induce estrogen effect and interfere with the function of the neuroendocrine system. The thyroid endocrine system (hypothalamic-pituitary-thyroid axis) is one of the main endocrine systems, and the mechanism of arsenic-induced thyroid endocrine toxicity is still unclear.

    Objective

    To investigate the effects of different arsenic exposure levels on estradiol (E2), hypothalamic thyrotropin-releasing hormone (TRH), and their receptor (ERα, ERβ, and TRHR) mRNAs in rats and the possible hypothalamic toxic pathway and mechanism.

    Methods

    Seventy Wister rats were randomly divided a control group (sterile water); low-, medium-, and high-dose arsenic exposure groups 0.8, 4.0, and 20.0 mg·kg−1 sodium arsenite (NaAsO2); estrogen receptor inhibitor (ICI182780) intervention + low-, medium-, and high-dose arsenic exposure groups; with 10 animals in each group, half male and half female. Rats in the arsenic exposure groups were exposed to NaAsO2 by drinking water for 19 weeks, and rats in the intervention groups were injected with 0.5 mg·kg−1 ICI182780 via tail vein at week 9, 3 times a week. The levels of E2 and TRH in serum of rats were detected by ELISA. The expression levels of estrogen receptor α (ERα), estrogen receptor β (ERβ), and TRH receptor (TRHR) mRNAs in hypothalamus of rats were detected by real-time PCR (RT-PCR).

    Results

    (1) E2 and its receptor mRNA: Compared with the control group, the serum E2 level of female rats was increased in the low-dose and the medium-dose arsenic exposure groups (P<0.05), and the serum E2 level of male rats was increased in the low-dose, the medium-dose, and the high-dose arsenic exposure groups (P<0.05), and the change of female E2 was greater than that of male rats. Compared with the control group, the relative expression levels of ERα mRNA and ERβ mRNA in female rats were increased in the low-dose, the medium-dose, and the high-dose arsenic exposure groups (P<0.05), so were the relative expression levels of ERα mRNA in male rats (P<0.05). (2) TRH and its receptor mRNA: Compared with the control group, the serum TRH level of female rats was increased in the high-dose arsenic group (P<0.05), the relative expression level of TRHR mRNA was increased in the low-dose, the medium-dose, and the high-dose arsenic exposure groups (P<0.05). Results (1) and results (2) suggested that females were more likely than males to have abnormal changes in E2, TRH, and related receptor genes after arsenic exposure. (3) Compared with female rats in the medium-high dose arsenic exposure group, the expressions of TRH and TRHR induced by arsenic exposure were inhibited after the intervention of ICI182780 (P<0.05), suggesting that arsenic in the hypothalamus may have toxic effects on TRH and TRHR by inducing estrogen-like effects.

    Conclusion

    Arsenic exposure can induce estrogen-like effects in the hypothalamus, interfere with thyroid function, and show dose-dependent and sex differences. E2 and TRH and their receptors may be the toxic pathway of arsenic-related estrogen-like effect.

     

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