Sexual Dimorphism of NADPH Oxidase/H₂O₂ System in Rat Thyroid Cells; Effect of Exogenous 17β-Estradiol

大鼠甲状腺细胞中 NADPH 氧化酶/H₂O₂ 系统的性别二态性;外源性 17β-雌二醇的影响

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Abstract

It has long been observed that females are more susceptible to thyroid diseases than males. Epidemiological and experimental data show that actions of hormonal factors-especially estrogens-may explain such disparity. However, the exact cause and mechanisms of this sexual dimorphism remain so far unknown. Therefore, we aimed at evaluating the effect of 17β-estradiol on the redox balance in thyroids of male and female rats. Expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, i.e., dual oxidase 1 (DUOX1), dual oxidase 2 (DUOX2) and NADPH oxidase 4 (NOX4), and hydrogen peroxide (H₂O₂) levels were evaluated in the primary cell cultures derived from thyroid glands of adult male or female Wistar rats. The measurement was made before and after treatment with 17β-estradiol alone or with addition of one of its receptor antagonists. We found that under basal conditions female thyroid cells are exposed to higher concentrations of H₂O₂, most likely due to NOX/DUOX enzymes activity. Additionally, exogenous 17β-estradiol stimulated NOX/DUOX expression as well as H₂O₂ production, and this effect was mainly mediated through ERα. In conclusion, oxidative processes may constitute mechanisms responsible for sexual dimorphism of thyroid diseases. Exogenous 17β-estradiol may play a crucial pathogenic role in thyroid diseases via oxidative mechanisms, however without any gender differences.

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