Institute for Biological Research 'Siniša Stanković', University of Belgrade, Belgrade, Serbia.
J Anat. 2018 Aug;233(2):204-212. doi: 10.1111/joa.12828. Epub 2018 May 14.
As a major phytoestrogen of soy, genistein effectively prevents bone loss in both humans and rat models of osteoporosis. However, although the bone-sparing effects of genistein are achieved directly through estrogen receptors, its mode of action on bone by modulation of other endocrine functions is not entirely clear. Thus, thyroid hormones and calcitonin (CT) have an essential influence on bone metabolism. Besides its action on bones, in this study we examined the effect of genistein on the activity of two different endocrine cell populations, thyroid follicular and C-cells. Fifteen-month-old Wistar rats were either bilaterally orchidectomized (Orx) or sham-operated (SO). Two weeks after surgery, half of the Orx rats were treated chronically with 30 mg kg b.w. genistein (Orx + G) subcutaneously (s.c.) every day for 3 weeks, while the remaining Orx rats and the SO rats were given the same volume of sterile olive oil to serve as controls. For histomorphometrical analysis of the trabecular bone microarchitecture an ImageJ public domain image processing programme was used. Thyroid sections were analysed histologically and stereologically after visualization of follicular and C-cells by immunohistochemical staining for thyroglobulin and CT. Thyroid follicular epithelium, interstitium, colloid and CT-immunopositive C-cells were examined morphometrically. Serum concentrations of osteocalcin (OC), triiodothyronine (T ), thyroxine (T ) and CT were determined as well as urinary calcium (Ca ) concentrations. Genistein treatment significantly increased cancellous bone area (B.Ar), trabecular thickness (TbTh) and trabecular number (TbN) (P < 0.05), but trabecular separation (Tb.Sp) was decreased (P < 0.05) compared with control Orx rats. In the thyroid, genistein treatment significantly elevated the relative volume density (Vv) of the follicular cells (P < 0.05) compared with Orx, whereas Vv of the colloid was lower (P < 0.05) than in the Orx. Evaluation of the biochemical parameters showed significant reductions in serum OC, T , T and urinary Ca concentrations (P < 0.05), compared with Orx rats. These data indicate that genistein treatment improves the trabecular microarchitecture of proximal tibia, induces histomorphometrical changes in thyroid glands, and decreases circulating thyroid hormone levels in orchidectomized rat model of male osteoporosis.
作为大豆中的一种主要植物雌激素，染料木黄酮有效地防止了骨质疏松症人类和大鼠模型中的骨质流失。然而，尽管染料木黄酮通过雌激素受体直接实现了保骨作用，但它通过调节其他内分泌功能对骨骼的作用方式尚不完全清楚。因此，甲状腺激素和降钙素 (CT) 对骨代谢有重要影响。除了对骨骼的作用外，在这项研究中，我们还研究了染料木黄酮对两种不同内分泌细胞群——甲状腺滤泡细胞和 C 细胞——活性的影响。15 月龄的 Wistar 大鼠要么双侧去势（Orx），要么假手术（SO）。手术后两周，一半的 Orx 大鼠每天皮下（s.c.）给予 30mg/kg 体重的染料木黄酮（Orx+G），持续 3 周，而其余的 Orx 大鼠和 SO 大鼠则给予相同体积的无菌橄榄油作为对照。使用 ImageJ 公共域图像处理程序对小梁骨微结构进行组织形态计量学分析。通过免疫组织化学染色甲状腺球蛋白和 CT 对甲状腺滤泡细胞和 C 细胞进行可视化后，对甲状腺切片进行组织学和体视学分析。对甲状腺滤泡上皮、间质、胶体和 CT 免疫阳性 C 细胞进行形态计量学检查。还测定了血清骨钙素（OC）、三碘甲状腺原氨酸（T₃）、甲状腺素（T₄）和 CT 的浓度以及尿钙（Ca）浓度。与对照 Orx 大鼠相比，染料木黄酮治疗显著增加了松质骨面积（B.Ar）、小梁厚度（TbTh）和小梁数量（TbN）（P<0.05），但小梁分离度（Tb.Sp）降低（P<0.05）。在甲状腺中，与 Orx 相比，染料木黄酮治疗显著增加了滤泡细胞的相对体积密度（Vv）（P<0.05），而胶体的 Vv 则低于 Orx（P<0.05）。生化参数评估显示，与 Orx 大鼠相比，血清 OC、T₃、T₄ 和尿 Ca 浓度显著降低（P<0.05）。这些数据表明，染料木黄酮治疗可改善胫骨近端小梁的微结构，诱导甲状腺组织形态计量学变化，并降低去势雄性骨质疏松症大鼠模型中循环甲状腺激素水平。
