title: Sexual dimorphism of thyroid reactive oxygen species production due to higher NADPH oxidase 4 expression in female thyroid glands.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratory of Molecular Radiobiology, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. rodrigof@biof.ufrj.br
authors.forename: Rodrigo Soares
authors.initials: RS
authors.lastname: Fortunato
authors.forename: William M O
authors.initials: WM
authors.lastname: Braga
authors.forename: Victor H
authors.initials: VH
authors.lastname: Ortenzi
authors.forename: Deivid C
authors.initials: DC
authors.lastname: Rodrigues
authors.forename: Bruno Moulin
authors.initials: BM
authors.lastname: Andrade
authors.forename: Leandro
authors.initials: L
authors.lastname: Miranda-Alves
authors.forename: Edson
authors.initials: E
authors.lastname: Rondinelli
authors.forename: Corinne
authors.initials: C
authors.lastname: Dupuy
authors.forename: Andrea Claudia Freitas
authors.initials: AC
authors.lastname: Ferreira
authors.forename: Denise P
authors.initials: DP
authors.lastname: Carvalho
mesh_terms: D000818:Animals; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D000074623:Dual Oxidases; D005260:Female; D005420:Flavoproteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012727:Sex Characteristics; D012741:Sexual Maturation; D013961:Thyroid Gland / Q000201:enzymology / Q000378:metabolism*; D000094765:Glutathione Peroxidase GPX1
chemical_list: D005420:Flavoproteins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D000074623:Dual Oxidases; C505355:GPX3 protein, rat; D002374:Catalase; D005979:Glutathione Peroxidase; C525844:glutathione peroxidase 2, rat; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498911:Nox4 protein, rat; C524752:Duox1 protein, rat; C486611:Duox2 protein, rat; D000094765:Glutathione Peroxidase GPX1; C000722069:Gpx1 protein, rat