Laboratório de Fisiologia e Sinalização Redox, Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Bloco G, sala G2-042, Av. Carlos Chagas Filho, 373, 21941-902, Rio de Janeiro, Brazil.
Laboratório de Fisiologia Endócrina Doris Rosenthal, Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Bloco G, sala G1-060, Av. Carlos Chagas Filho, 373, 21941-902, Rio de Janeiro, Brazil.
Mol Cell Endocrinol. 2022 Apr 15;546:111593. doi: 10.1016/j.mce.2022.111593. Epub 2022 Feb 6.
Thyroid diseases are more prevalent in women, and this difference seems to be associated with the oxidative stress found in the thyroid of females. Thyroid NADPH Oxidase 4 (NOX4) was shown to respond to estrogen, which can also modulate TGF-β1, a potent stimulator of NOX4. This study aimed to investigate the effects of TGF-β1 on redox homeostasis parameters in the rat thyroid cell PCCL3 and the interrelationship between estrogen and TGF-β1. TGF-β1 treatment increased both intra- and extracellular ROS generation along with NOX4 expression and reduced GPX and catalase activities, extracellular H2O2 scavenging capacity, and reduced thiol content. TGF-β1 mRNA and protein expression are higher in female thyroid glands of rats in comparison to males. Moreover, 17β-estradiol treatment enhanced TGF-β1 mRNA in PCCL3 cells, decreased extracellular bioavailability but did not activate Smad pathway. Our data suggest that higher levels of TGF-β1 in females are potentially related to higher ROS availability which may be associated with the sex disparity in thyroid disorders.
甲状腺疾病在女性中更为普遍，这种差异似乎与女性甲状腺中的氧化应激有关。甲状腺 NADPH 氧化酶 4（NOX4）对雌激素有反应，雌激素也可以调节 TGF-β1，TGF-β1 是 NOX4 的一种强有力的刺激物。本研究旨在探讨 TGF-β1 对大鼠甲状腺细胞 PCCL3 中氧化还原平衡参数的影响，以及雌激素和 TGF-β1 之间的相互关系。TGF-β1 处理增加了细胞内和细胞外 ROS 的产生，同时增加了 NOX4 的表达，并降低了 GPX 和过氧化氢酶的活性、细胞外 H2O2 的清除能力和巯基含量。与雄性大鼠相比，雌性大鼠甲状腺中的 TGF-β1 mRNA 和蛋白表达水平更高。此外，17β-雌二醇处理增强了 PCCL3 细胞中的 TGF-β1 mRNA，降低了细胞外生物利用度，但没有激活 Smad 通路。我们的数据表明，女性中更高水平的 TGF-β1 可能与更高的 ROS 可用性有关，这可能与甲状腺疾病中的性别差异有关。
