Grupo de Pesquisa, Desenvolvimento e Inovação em Endocrinologia Experimental-GPDIEEx, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Brazil; Pós-graduação em Endocrinologia, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Brazil; Laboratório de Fisiologia Endócrina Doris Rosenthal, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil.
Grupo de Pesquisa, Desenvolvimento e Inovação em Endocrinologia Experimental-GPDIEEx, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Brazil; Pós-graduação em Endocrinologia, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Brazil; Pós-graduação em Farmacologia e Química Medicinal, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Brazil.
Mol Cell Endocrinol. 2018 Jan 15;460:246-257. doi: 10.1016/j.mce.2017.07.038. Epub 2017 Jul 31.
Endocrine disruptors (EDs), chemical substances widely used in industry and ubiquitously distributed in the environment, are able to interfere with the synthesis, release, transport, metabolism, receptor binding, action, or elimination of endogenous hormones. EDs affect homeostasis mainly by acting on nuclear and nonnuclear steroid receptors but also on serotonin, dopamine, norepinephrine and orphan receptors in addition to thyroid hormone receptors. Tributyltin (TBT), an ED widely used as a pesticide and biocide in antifouling paints, has well-documented actions that include inhibiting aromatase and affecting the nuclear receptors PPARγ and RXR. TBT exposure in humans and experimental models has been shown to mainly affect reproductive function and adipocyte differentiation. Since thyroid hormones play a fundamental role in regulating the basal metabolic rate and energy homeostasis, it is crucial to clarify the effects of TBT on the hypothalamus-pituitary-thyroid axis. Therefore, we review herein the main effects of TBT on important metabolic pathways, with emphasis on disruption of the thyroid axis that could contribute to the development of endocrine and metabolic disorders, such as insulin resistance and obesity.
内分泌干扰物（EDs）是一种广泛应用于工业生产且在环境中普遍存在的化学物质，它们能够干扰内源性激素的合成、释放、运输、代谢、受体结合、作用或消除。EDs 主要通过作用于核受体和非核甾体受体，还通过作用于 5-羟色胺、多巴胺、去甲肾上腺素和孤儿受体以及甲状腺激素受体来影响体内平衡。三丁基锡（TBT）是一种被广泛用作防污漆中的杀虫剂和杀生剂的 ED，其具有抑制芳香酶和影响核受体 PPARγ 和 RXR 等作用已被充分证实。人类和实验模型中的 TBT 暴露已被证明主要影响生殖功能和脂肪细胞分化。由于甲状腺激素在调节基础代谢率和能量平衡方面起着至关重要的作用，因此必须阐明 TBT 对下丘脑-垂体-甲状腺轴的影响。因此，我们在此综述了 TBT 对重要代谢途径的主要影响，重点讨论了甲状腺轴的紊乱，这可能导致内分泌和代谢紊乱的发生，如胰岛素抵抗和肥胖。
