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紫外线过滤剂桂皮酸盐(OMC)连续5天治疗对大鼠下丘脑-垂体-甲状腺功能的影响。

Effects of a 5-day treatment with the UV-filter octyl-methoxycinnamate (OMC) on the function of the hypothalamo-pituitary-thyroid function in rats.

作者信息

Klammer Holger, Schlecht Christiane, Wuttke Wolfgang, Schmutzler Cornelia, Gotthardt Inka, Köhrle Josef, Jarry Hubertus

机构信息

Department of Clinical and Experimental Endocrinology, University of Goettingen, Robert-Koch-Str. 40, 37075 Goettingen, Germany.

出版信息

Toxicology. 2007 Sep 5;238(2-3):192-9. doi: 10.1016/j.tox.2007.06.088. Epub 2007 Jun 23.

Abstract

Octyl-methoxycinnamate (OMC) is one of the most frequently used UV-filters in sunscreens to protect the skin against the noxious influence of UV radiation. Recently, OMC was suspected to act as an "endocrine active chemical" (EAC) with estrogenic actions. While EACs have been investigated thoroughly for interference with reproductive function in mammalians, surprisingly little efforts have been made to investigate an interference of EACs with the hypothalamo-pituitary-thyroid (HPT) axis despite the expression of estrogen receptors in all parts of this axis. Therefore, we conducted an in vivo study with ovariectomised rats treated for 5 days with different doses of OMC or 17beta-estradiol (E2) as a control. Determined parameters comprised serum levels of TSH, T4 and T3, hypothalamic TRH mRNA expression, protein-expression of the sodium-iodide-symporter (NIS) and the TSH receptor and the activities of thyroid peroxidase (TPO) in the thyroid and the T3-responsive hepatic type I 5'deiodinase (Dio1) in the liver. While E2 did not affect TSH-, T4- or T3-levels, OMC caused a dose-dependent decrease of serum concentrations of all of these hormones. TRH expression remained unaffected, while in the thyroid, expression of the TSH receptor but not of NIS was stimulated by OMC. TPO activity was unaltered but Dio1 activity was reduced by OMC. Thus, our results demonstrate a non-estrogenic interference of OMC within the rodent HPT axis with inadequate feedback response to impaired thyroid hormone status, indicated by decreased serum thyroid hormone and hepatic Dio1 levels.

摘要

桂皮酸盐(OMC)是防晒霜中最常用的紫外线过滤剂之一,用于保护皮肤免受紫外线辐射的有害影响。最近,OMC被怀疑是一种具有雌激素作用的“内分泌活性化学物质”(EAC)。虽然已经对EACs干扰哺乳动物生殖功能进行了深入研究,但令人惊讶的是,尽管该轴的所有部分都表达雌激素受体,但对EACs干扰下丘脑 - 垂体 - 甲状腺(HPT)轴的研究却很少。因此,我们对去卵巢大鼠进行了一项体内研究,用不同剂量的OMC或17β-雌二醇(E2)作为对照处理5天。测定的参数包括血清促甲状腺激素(TSH)、甲状腺素(T4)和三碘甲状腺原氨酸(T3)水平、下丘脑促甲状腺激素释放激素(TRH)mRNA表达、钠 - 碘转运体(NIS)和TSH受体的蛋白表达,以及甲状腺中甲状腺过氧化物酶(TPO)的活性和肝脏中T3反应性肝I型5'脱碘酶(Dio1)的活性。虽然E2不影响TSH、T4或T3水平,但OMC导致所有这些激素的血清浓度呈剂量依赖性下降。TRH表达未受影响,而在甲状腺中,OMC刺激TSH受体的表达,但不刺激NIS的表达。TPO活性未改变,但OMC降低了Dio1活性。因此,我们的结果表明,OMC在啮齿动物HPT轴内具有非雌激素干扰作用,对甲状腺激素状态受损的反馈反应不足,表现为血清甲状腺激素和肝脏Dio1水平降低。

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