雌激素和选择性雌激素受体调节剂可上调去卵巢大鼠甲状腺血管内皮生长因子和一氧化氮合酶 III 的表达。
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.
机构信息
Department of Endocrinology, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
出版信息
Thyroid. 2010 Jan;20(1):85-92. doi: 10.1089/thy.2009.0246.
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.
背景
雌激素促进甲状腺细胞的生长。因此，我们分析了雌激素和选择性雌激素受体调节剂（SERM）对去卵巢（Ovx）大鼠甲状腺中血管内皮生长因子（VEGF）和一氧化氮合酶 III（NOS III）表达的影响。
方法
将 Wistar 大鼠分为五组，除了假手术对照（Sham）组外，均进行双侧卵巢切除术。大鼠分组如下：Sham 组；Ovx 组；Ovx 组大鼠每天皮下注射苯甲酸雌二醇 3.5μg/kg、他莫昔芬 2.5mg/kg 或雷洛昔芬 2.5mg/kg，连续 50 天。对照组动物给予丙二醇，治疗结束时处死大鼠。切除甲状腺，称重，并进行免疫组织化学分析 VEGF 或 NOS III 的表达。通过免疫检测α-平滑肌肌动蛋白评估平均血管面积。
结果
与 Sham 组相比，Ovx 组甲状腺重量和平均血管面积降低（p<0.01）。与 Sham 组、Ovx+苯甲酸雌二醇组、Ovx+他莫昔芬组或 Ovx+雷洛昔芬组相比，Ovx 组 VEGF（p<0.01）和 NOS III 表达（p<0.05）显著降低。VEGF 和 NOS III 的免疫反应性主要在滤泡上皮细胞的细胞质中检测到。
结论
我们的数据表明，雌激素和 SERM 调节甲状腺血管生成，他莫昔芬和雷洛昔芬的作用类似于雌激素。雌激素和 SERM 通过上调 VEGF 和 NOS III，逆转了在 Ovx 大鼠甲状腺微血管中观察到的影响。
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