title: Expressions of vascular endothelial growth factor and nitric oxide synthase III in the thyroid gland of ovariectomized rats are upregulated by estrogen and selective estrogen receptor modulators.
abstract: BACKGROUND
  Estrogen promotes the growth of thyroid cells. Therefore, we analyzed the influence of estrogen and selective estrogen receptor modulators (SERMs) on the expression of vascular endothelial growth factor (VEGF) and nitric oxide synthase III (NOS III) in the thyroid gland of ovariectomized (Ovx) rats.
  
  
  METHODS
  Wistar rats were divided into five groups, and bilateral ovariectomies were performed, except on the Sham-operated controls (Sham). Rats were grouped as follows: Sham; Ovx; and Ovx rats treated with daily subcutaneous injections of estradiol benzoate 3.5 microg/kg, tamoxifen 2.5 mg/kg, or raloxifene 2.5 mg/kg for 50 consecutive days. Control animals received vehicle (propyleneglycol), and at the end of the treatment, rats were sacrificed. The thyroid glands were excised, weighed, and processed for analysis of the expression of VEGF or NOS III by immunohistochemistry. The mean vascular areas were evaluated by immunodetection of alpha-smooth muscle actin.
  
  
  RESULTS
  Thyroid weight and mean vascular area were lower in Ovx as compared with Sham, Ovx + estradiol benzoate, Ovx + Tam, or Ovx + Ral (p < 0.01). VEGF (p < 0.01) and NOS III expressions (p < 0.05) were significantly lower in the Ovx group, as compared with Sham, Ovx + estradiol benzoate, Ovx + Tam, and Ovx + Ral. Immunoreactivity for both VEGF and NOS III was mainly detected in the cytoplasm of the follicular epithelial cells.
  
  
  CONCLUSIONS
  Our data suggest that estrogen and SERMs regulate the thyroid gland vascularization and that tamoxifen and raloxifene behave like estrogen does. Estrogen and SERMs upregulate VEGF and NOS III in such a way as to reverse the effects detected on the thyroid microvasculature of the Ovx rats.
authors.affiliation: Department of Endocrinology, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. lfbita@gmail.com
authors.forename: Luiz Felipe Bittencourt
authors.initials: LF
authors.lastname: de Araujo
authors.forename: Renata
authors.initials: R
authors.lastname: Grozovsky
authors.forename: Mário José
authors.initials: MJ
authors.lastname: dos Santos Pereira
authors.forename: Jorge José
authors.initials: JJ
authors.lastname: de Carvalho
authors.forename: Mário
authors.initials: M
authors.lastname: Vaisman
authors.forename: Denise P
authors.initials: DP
authors.lastname: Carvalho
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D007150:Immunohistochemistry; D055806:Microvessels / Q000187:drug effects; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D009929:Organ Size; D010052:Ovariectomy; D020849:Raloxifene Hydrochloride / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D013629:Tamoxifen / Q000494:pharmacology; D013961:Thyroid Gland / Q000098:blood supply / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects*; D014599:Uterus / Q000033:anatomy & histology / Q000187:drug effects; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism*
chemical_list: D000199:Actins; D004958:Estradiol; D004967:Estrogens; D052250:Nitric Oxide Synthase Type III; D020849:Raloxifene Hydrochloride; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; D042442:Vascular Endothelial Growth Factors; C498862:Acta2 protein, rat; C074283:estradiol 3-benzoate