Laboratory of Molecular Radiobiology, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Thyroid. 2013 Jan;23(1):111-9. doi: 10.1089/thy.2012.0142.
Dual oxidases (DUOX1 and DUOX2) are NADPH oxidases (NOX) involved in hydrogen peroxide production necessary for thyroid hormonogenesis, but recently, the NOX4 has also been described in the thyroid gland. The prevalence of thyroid disease is higher in women, and the basis for this difference might involve a higher oxidative stress level in the female thyroid gland. Hence, we aimed at evaluating whether the function and the expression of enzymes involved in the thyroid redox balance differ between females and males.
DUOX1, DUOX2, NOX4, glutathione peroxidase (GPx), and catalase activities and expression levels were evaluated in the thyroids of prepubertal and adult male and female rats. The mRNA levels of DUOXA1 and DUOXA2, the DUOX maturation factors, and of p22phox and Poldip2 (subunits of NOX4) were also determined.
A higher calcium-independent H(2)O(2) production was detected in the adult female rat thyroid, being higher in the estrous phase of the cycle. Moreover, the expression of NOX4 and Poldip2 mRNA was higher in the thyroids of adult female rats, as well as in PCCL3 cells treated with 17β-estradiol. The GPx1 mRNA expression was higher in adult female thyroids, while GPx2 and GPx3 mRNA and total GPx activity were not significantly different. Catalase mRNA expression and activity, together with thyroid thiol levels were significantly lower in the adult female rat thyroid.
Taken together, our results show that the thyroid gland of female rats is exposed to higher oxidative stress levels due both to increased reactive oxygen species (ROS) production through NOX4, and decreased ROS degradation.
双氧化酶（DUOX1 和 DUOX2）是参与甲状腺激素生成所必需的过氧化氢产生的 NADPH 氧化酶（NOX），但最近，甲状腺中也描述了 NOX4。女性中甲状腺疾病的患病率更高，这种差异的基础可能涉及女性甲状腺中的氧化应激水平更高。因此，我们旨在评估参与甲状腺氧化还原平衡的酶的功能和表达是否在男性和女性之间存在差异。
评估了幼年期和成年期雄性和雌性大鼠甲状腺中的 DUOX1、DUOX2、NOX4、谷胱甘肽过氧化物酶 (GPx) 和过氧化氢酶活性和表达水平。还测定了 DUOXA1 和 DUOXA2（DUOX 成熟因子）以及 p22phox 和 Poldip2（NOX4 的亚单位）的 mRNA 水平。
在成年雌性大鼠甲状腺中检测到更高的钙非依赖性 H2O2 产生，在周期的发情期更高。此外，NOX4 和 Poldip2 mRNA 的表达在成年雌性大鼠的甲状腺中更高，以及用 17β-雌二醇处理的 PCCL3 细胞中更高。成年雌性大鼠甲状腺中的 GPx1 mRNA 表达较高，而 GPx2 和 GPx3 mRNA 及总 GPx 活性无明显差异。成年雌性大鼠甲状腺中的过氧化氢酶 mRNA 表达和活性以及甲状腺硫醇水平显著降低。
综上所述，我们的结果表明，由于 NOX4 导致活性氧 (ROS) 产生增加，以及 ROS 降解减少，雌性大鼠的甲状腺暴露于更高的氧化应激水平。
