Filipović Branko, Šošić-Jurjević Branka, Ajdžanović Vladimir, Živanović Jasmina, Isenović Esma, Popovska-Perčinić Florina, Milošević Verica
Institute for Biological Research ″Siniša Stanković″, University of Belgrade, Belgrade, Serbia.
Vinca Institute of Nuclear Science, Laboratory for Molecular Genetics and Radiobiology, University of Belgrade, Belgrade, Serbia.
J Anat. 2015 May;226(5):489-96. doi: 10.1111/joa.12298. Epub 2015 Apr 7.
Thyroid C-cells produce calcitonin (CT), a hypocalcemic hormone, that acts as an inhibitor of bone resorption. In this study, we investigated the effects of tamoxifen (TAM) as a selective estrogen receptor modulator on thyroid C-cells, trabecular bone and biochemical markers of bone metabolism in an animal model of androgen deficiency, represented by middle-aged orchidectomized (Orx) rats. Fifteen-month-old male Wistar rats were divided into: Orx and sham-operated (SO) groups. Rats from one Orx group were injected subcutaneously with TAM citrate (Orx + TAM; 0.3 mg kg(-1) b.w.), while the rats from SO and a second Orx group received vehicle alone, once a day for 3 weeks. The peroxidase-antiperoxidase method was applied for localization of CT in C-cells. Thyroid C-cells were morphometrically and ultrastructurally analyzed. An ImageJ image-processing program was used to measure bone histomorphometric parameters. Blood serum samples were analyzed for CT, osteocalcin (OC), calcium (Ca2+ ) and phosphorus (P). Urinary Ca2+ concentrations were measured. TAM treatment significantly increased thyroid C-cell volume (Vc ) and serum CT when compared with vehicle-treated Orx rats. Analysis of trabecular microarchitecture of the tibia showed that administration of TAM significantly increased cancellous bone area, trabecular thickness and trabecular number, whereas trabecular separation was significantly decreased compared with vehicle-treated Orx rats. Serum OC and urinary Ca2+ concentrations were significantly lower in comparison with the control Orx group. These results indicate that in our rat model of androgen deficiency, TAM stimulated calcitonin-producing thyroid C-cells and increased trabecular bone mass.
甲状腺C细胞产生降钙素（CT），这是一种降钙激素，可作为骨吸收的抑制剂。在本研究中，我们以中年去势（Orx）大鼠为雄激素缺乏动物模型，研究了他莫昔芬（TAM）作为选择性雌激素受体调节剂对甲状腺C细胞、小梁骨和骨代谢生化标志物的影响。将15月龄雄性Wistar大鼠分为：去势组和假手术（SO）组。一组去势大鼠皮下注射柠檬酸他莫昔芬（去势 + TAM；0.3 mg kg⁻¹体重），而假手术组和另一组去势大鼠仅接受溶剂，每天一次，共3周。采用过氧化物酶-抗过氧化物酶法对C细胞中的CT进行定位。对甲状腺C细胞进行形态计量学和超微结构分析。使用ImageJ图像处理程序测量骨组织形态计量学参数。分析血清样本中的CT、骨钙素（OC）、钙（Ca²⁺）和磷（P）。测量尿Ca²⁺浓度。与溶剂处理的去势大鼠相比，TAM治疗显著增加了甲状腺C细胞体积（Vc）和血清CT。胫骨小梁微结构分析表明，与溶剂处理的去势大鼠相比，TAM给药显著增加了松质骨面积、小梁厚度和小梁数量，而小梁间距显著减小。与对照组去势组相比，血清OC和尿Ca²⁺浓度显著降低。这些结果表明，在我们的雄激素缺乏大鼠模型中，TAM刺激了产生降钙素的甲状腺C细胞并增加了小梁骨量。
