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青春期前大豆异黄酮的摄入可导致雄性 Wistar 大鼠亚临床甲状腺功能减退症。

Peripubertal soy isoflavone consumption leads to subclinical hypothyroidism in male Wistar rats.

机构信息

Department of Medicine, State University of Centro-Oeste (UNICENTRO), Rua Simeão Camargo Varela de Sa, 03, Zip-Code 85040-080, Parana, Brazil.

Department of Veterinary Medicine, State University of Centro-Oeste (UNICENTRO), Rua Simeão Camargo Varela de Sa, 03, Zip-Code 85040-080, Parana, Brazil.

出版信息

J Dev Orig Health Dis. 2023 Apr;14(2):209-222. doi: 10.1017/S2040174422000496. Epub 2022 Aug 26.

DOI:10.1017/S2040174422000496
PMID:36017706
Abstract

Exposure to endocrine-disrupting chemicals during critical windows of development may lead to functional abnormalities in adulthood. Isoflavones are a flavonoid group of phytoestrogens that are recognized by their estrogenic activity and are highly abundant in soybean. Since the thyroid gland presents estrogen receptors and infants, toddlers and teenagers may consume isoflavones from soy-based infant formula and beverages as alternatives to animal milk, we propose to investigate the potential effects of relevant concentrations of soy isoflavones in the regulation of the hypothalamic-pituitary (HP) thyroid axis using peripubertal male rats as an experimental model. Thirty-two 23-day-old male rats were exposed to 0.5, 5, or 50 mg of soy isoflavones/kg from weaning to 60 days of age, when they were euthanized, and the tissues were collected to evaluate the mRNA expression of genes involved in the regulation of the HP thyroid axis and dosages of thyroid hormones (THs). Serum TSH concentrations were increased, while alterations were not observed in serum concentrations of triiodothyronine and thyroxine. Regarding mRNA gene expression, was increased in the hypothalamus, , , and were decreased in the pituitary, and and were reduced in the thyroid. In the heart, and were increased, and was decreased. In the liver, , , and were decreased. These results suggest that the consumption of relevant doses of soy isoflavones during the peripubertal period in males may induce subclinical hypothyroidism, with alterations in the regulation of the HP thyroid axis, modulation of TH synthesis, and peripheral alterations in TH target organs.

摘要

在发育关键期暴露于内分泌干扰化学物质可能导致成年后的功能异常。异黄酮是植物雌激素类黄酮的一个群组,因其雌激素活性而被识别,并且在大豆中含量非常丰富。由于甲状腺存在雌激素受体,婴儿、幼儿和青少年可能会从大豆配方奶和饮料中摄取异黄酮,作为动物奶的替代品,因此我们建议使用青春期前雄性大鼠作为实验模型,研究相关浓度的大豆异黄酮对下丘脑-垂体(HP)甲状腺轴的调节作用。32 只 23 天大的雄性大鼠从断奶到 60 天大时,分别暴露于 0.5、5 或 50mg/kg 的大豆异黄酮,然后进行安乐死,收集组织以评估参与 HP 甲状腺轴调节的基因的 mRNA 表达和甲状腺激素(THs)的剂量。血清 TSH 浓度升高,而三碘甲状腺原氨酸和甲状腺素的血清浓度没有变化。关于 mRNA 基因表达,下丘脑 增加,垂体 减少,甲状腺 减少。心脏中 增加, 减少。肝脏中 减少。这些结果表明,在青春期前雄性大鼠中摄入相关剂量的大豆异黄酮可能会导致亚临床甲状腺功能减退,同时影响 HP 甲状腺轴的调节、TH 合成的调节以及 TH 靶器官的外周改变。

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