title: Sexual dimorphism and thyroid dysfunction: a matter of oxidative stress?
abstract: Thyroid diseases, such as autoimmune disease and benign and malignant nodules, are more prevalent in women than in men, but the mechanisms involved in this sex difference is still poorly defined. H₂O₂ is produced at high levels in the thyroid gland and regulates parameters such as cell proliferation, migration, survival, and death; an imbalance in the cellular oxidant-antioxidant system in the thyroid may contribute to the greater incidence of thyroid disease among women. Recently, we demonstrated the existence of a sexual dimorphism in the thyrocyte redox balance, characterized by higher H₂O₂ production, due to higher NOX4 and Poldip2 expression, and weakened enzymatic antioxidant defense in the thyroid of adult female rats compared with male rats. In addition, 17β-estradiol administration increased NOX4 mRNA expression and H₂O₂ production in thyroid PCCL3 cells. In this review, we discuss the possible involvement of oxidative stress in estrogen-related thyroid pathophysiology. Our current hypothesis suggests that a redox imbalance elicited by estrogen could be involved in the sex differences found in the prevalence of thyroid dysfunctions.
authors.affiliation: Laboratory of Molecular Radiobiology, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Avenida Carlos Chagas Filho, 373, CCS - Bloco G - Subsolo - Sala G0-031, Cidade Universitária - Ilha do Fundão, 21941-902 Rio de Janeiro, RJ, Brazil Laboratory of Endocrine Physiology, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil Mixed Unity of Research (UMR) 8200 - Genomes and Cancer, The Gustave Roussy Institute of Integrated Cancer Research, Villejuif F-94805, France.
authors.forename: Rodrigo S
authors.initials: RS
authors.lastname: Fortunato
authors.forename: Andrea C F
authors.initials: AC
authors.lastname: Ferreira
authors.forename: Fabio
authors.initials: F
authors.lastname: Hecht
authors.forename: Corinne
authors.initials: C
authors.lastname: Dupuy
authors.forename: Denise P
authors.initials: DP
authors.lastname: Carvalho
mesh_terms: D000818:Animals; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D011960:Receptors, Estrogen / Q000378:metabolism*; D012727:Sex Characteristics; D013959:Thyroid Diseases / Q000209:etiology* / Q000378:metabolism; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism*
chemical_list: D004967:Estrogens; D011960:Receptors, Estrogen
keywords: NADPH oxidases; estrogen; reactive oxygen species; thyroid