title: Sex hormones modulate circulating antioxidant enzymes: impact of estrogen therapy.
abstract: OBJECTIVE
  Ovarian senescence affects many tissues and produces a variety of symptoms and signs. We hypothesized that estrogens may also influence circulating redox balance by regulating activity of the cellular antioxidative enzyme system. We aimed to explore the impact of surgical estrogen deprivation and replacement (ERT) on the glutathione balance and antioxidant enzymes expression in fertile women.
  
  
  METHODS
  Nineteen healthy premenopausal women who underwent total hysterectomy with bilateral salpingo-oophorectomy were evaluated at baseline, 30 days after surgery without ERT and 30 days after ERT. Redox balance was determined by measuring blood reduced (GSH) and oxidized (GSSG) glutathione, as well as the GSSG/GSH ratio. Antioxidant status was evaluated by measuring serum estrogen (E2) levels and mRNA expression of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione S-transferase (GST) in peripheral blood mononuclear cells.
  
  
  RESULTS
  Serum E2 significantly lowered after surgery, and increased in 12 out of 19 patients after 30 days of ERT (Responders). In such patients, an increase in oxidative stress was observed after surgery that resolved after ERT. Oxidative stress was sustained by reduction in the mRNA expression of both SOD and GSH-Px, that recovered after 30 days of therapy in responders. CAT and GST mRNA expression were not modified by surgery and replacement therapy.
  
  
  CONCLUSIONS
  Menopause is associated with significant change in antioxidant gene expression that in turn affects circulating redox state. Estrogens replacement therapy is able to prevent and counteract such modifications by acting as regulators of key antioxidant gene expression. These findings suggest that antioxidant genes are, almost in part, under the control of sex hormones, and that pathophysiology of the difference in gender disease may depend on the redox biology.
authors.affiliation: Department of Medical and Surgical Sciences, Institute of Internal Medicine, University of Foggia, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Bellanti
authors.forename: Maria
authors.initials: M
authors.lastname: Matteo
authors.forename: Tiziana
authors.initials: T
authors.lastname: Rollo
authors.forename: Filomena
authors.initials: F
authors.lastname: De Rosario
authors.forename: Pantaleo
authors.initials: P
authors.lastname: Greco
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Vendemiale
authors.forename: Gaetano
authors.initials: G
authors.lastname: Serviddio
mesh_terms: D000975:Antioxidants / Q000378:metabolism*; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000008:administration & dosage* / Q000097:blood; D005260:Female; D005786:Gene Expression Regulation; D005978:Glutathione / Q000097:blood*; D006801:Humans; D007044:Hysterectomy; D008875:Middle Aged; D010052:Ovariectomy; D010084:Oxidation-Reduction; D017697:Premenopause / Q000097:blood*
chemical_list: D000975:Antioxidants; D004967:Estrogens; D005978:Glutathione
keywords: Estrogen replacement therapy; Glutathione; Menopause; Oxidative stress
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