PMID- 20017619 OWN - NLM STAT- MEDLINE DCOM- 20100408 LR - 20151119 IS - 1557-9077 (Electronic) IS - 1050-7256 (Linking) VI - 20 IP - 1 DP - 2010 Jan TI - 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. PG - 85-92 LID - 10.1089/thy.2009.0246 [doi] AB - 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. FAU - de Araujo, Luiz Felipe Bittencourt AU - de Araujo LF AD - Department of Endocrinology, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. lfbita@gmail.com FAU - Grozovsky, Renata AU - Grozovsky R FAU - dos Santos Pereira, Mario Jose AU - dos Santos Pereira MJ FAU - de Carvalho, Jorge Jose AU - de Carvalho JJ FAU - Vaisman, Mario AU - Vaisman M FAU - Carvalho, Denise P AU - Carvalho DP LA - eng PT - Journal Article PL - United States TA - Thyroid JT - Thyroid : official journal of the American Thyroid Association JID - 9104317 RN - 0 (Actins) RN - 0 (Estrogens) RN - 0 (Selective Estrogen Receptor Modulators) RN - 0 (Vascular Endothelial Growth Factors) RN - 0 (smooth muscle actin, rat) RN - 094ZI81Y45 (Tamoxifen) RN - 1S4CJB5ZGN (estradiol 3-benzoate) RN - 4F86W47BR6 (Raloxifene Hydrochloride) RN - 4TI98Z838E (Estradiol) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type III) SB - IM MH - Actins/metabolism MH - Animals MH - Estradiol/*analogs & derivatives/pharmacology MH - Estrogens/*pharmacology MH - Female MH - Immunohistochemistry MH - Microvessels/drug effects MH - Nitric Oxide Synthase Type III/*metabolism MH - Organ Size MH - Ovariectomy MH - Raloxifene Hydrochloride/pharmacology MH - Random Allocation MH - Rats MH - Rats, Wistar MH - Selective Estrogen Receptor Modulators/*pharmacology MH - Tamoxifen/pharmacology MH - Thyroid Gland/blood supply/cytology/drug effects/*metabolism MH - Up-Regulation/*drug effects MH - Uterus/anatomy & histology/drug effects MH - Vascular Endothelial Growth Factors/*metabolism EDAT- 2009/12/19 06:00 MHDA- 2010/04/09 06:00 CRDT- 2009/12/19 06:00 PHST- 2009/12/19 06:00 [entrez] PHST- 2009/12/19 06:00 [pubmed] PHST- 2010/04/09 06:00 [medline] AID - 10.1089/thy.2009.0246 [doi] PST - ppublish SO - Thyroid. 2010 Jan;20(1):85-92. doi: 10.1089/thy.2009.0246.