Thyrotropin, traditionally seen as a pituitary hormone that regulates thyroid glands, has additional roles in physiology including skeletal remodeling. Population-based observations in subjects with euthyroidism or subclinical hyperthyroidism indicated a negative association between bone mass and low-normalTSH. The findings of correlative studies were supported by small intervention trials using recombinant human TSH (rhTSH) injection, and genetic and case-based evidence. Genetically-modified mouse models, which disrupt the reciprocal relationship between TSH and thyroid hormone, have allowed us to examine an independent role of TSH. Since the first description of osteoporotic phenotype in haploinsufficient Tshr ^+/- mice with normal thyroid hormone levels, the anti–osteoclastic effect of TSH has been documented in in vitro and in vivo studies. Further studies showed that increased osteoclastogenesis in Tshr–deficient mice was mediated by TNFα. Low TSH not only increased osteoclastogenesis, but also decreased osteoblastogenesis in bone marrow–derived primary osteoblast cultures. However, later in vivo studies using small and intermittent dose of rhTSH showed pro-anabolic effect, which suggests that its action might be dose- and frequency-dependent. TSHR was shown to interact with IGF1R, and VEGF and Wnt pathway might play a role in TSH effect on osteoblasts. The expression and direct skeletal effect of a biologically active splice variant of TSHβ subunit (TSHβv) in bone-marrow-derived macrophage and other immune cells suggest local skeletal effect of TSHR. Further studies of how locally secreted TSHβv and systemic TSHβ interact in skeletal remodeling through the endocrine, immune and skeletal system will help us better understand the hyperthyroidism-induced bone disease.

中文翻译：

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TSH、甲亢和骨量

促甲状腺激素，传统上被视为调节甲状腺的垂体激素，在生理学中具有额外的作用，包括骨骼重塑。对甲状腺功能正常或亚临床甲状腺功能亢进症受试者的基于人群的观察表明，骨量与正常低水平 TSH 呈负相关。相关研究的结果得到了使用重组人促甲状腺激素 (rhTSH) 注射的小型干预试验以及遗传和基于病例的证据的支持。转基因小鼠模型破坏了 TSH 和甲状腺激素之间的相互关系，使我们能够检查 TSH 的独立作用。自首次描述单倍体Tshr ^{+/-骨质疏松表型以来}对于甲状腺激素水平正常的小鼠，TSH 的抗破骨作用已在体外和体内研究中得到证实。进一步的研究表明，Tshr 缺陷小鼠的破骨细胞生成增加是由 TNFα 介导的。低 TSH 不仅增加了破骨细胞生成，而且减少了骨髓来源的原代成骨细胞培养物中的成骨细胞生成。然而，后来在体内使用小剂量和间歇剂量的 rhTSH 的研究显示促合成代谢作用，这表明它的作用可能是剂量和频率依赖性的。TSHR 显示​​与 IGF1R 相互作用，VEGF 和 Wnt 通路可能在 TSH 对成骨细胞的作用中发挥作用。TSHβ 亚基 (TSHβv) 的生物活性剪接变体在骨髓来源的巨噬细胞和其他免疫细胞中的表达和直接骨骼效应表明 TSHR 的局部骨骼效应。进一步研究局部分泌的 TSHβv 和全身 TSHβ 如何通过内分泌、免疫和骨骼系统在骨骼重塑中相互作用，将有助于我们更好地了解甲亢引起的骨病。