Regulation of the gp80 and gp130 subunits of the IL-6 receptor by sex steroids in the murine bone marrow
Regulation of the gp80 and gp130 subunits of the IL-6 receptor by sex steroids in the murine bone marrow
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DOI：
10.1172/jci119729
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发表时间：
1997-10-15
影响因子：
15.9
通讯作者：
Manolagas, SC
中科院分区：
文献类型：
--
作者：
Lin, SC;Yamate, T;Manolagas, SC
雌激素和雄激素至少部分通过抑制IL-6的产生，从而抑制破骨细胞生成来发挥其抗骨质疏松作用。然而，一些观察结果表明，除了增加IL-6的生产，破骨细胞的过程中，这种细胞因子的敏感性改变卵巢切除术后。基于此以及IL-6受体的配体结合亚基（gp 80）是IL-6对骨作用的限制因素的证据，假设性类固醇也调节IL-6受体的表达。我们报告说，17 β-雌二醇或双氢睾酮在体外减少的gp 80 mRNA的丰度，以及IL-6受体（gp 130）在骨髓基质/成骨细胞系细胞的信号转导亚基的mRNA，也降低gp 130蛋白水平。这些效应不需要新的蛋白质合成。与性类固醇相反，甲状旁腺激素刺激gp 130的表达，这种作用是反对性类固醇。与这些发现一致，小鼠卵巢切除术引起gp 80，gp 130和IL-6 mRNA在离体骨髓细胞培养物中的表达增加，如通过定量逆转录（RT）-PCR测定的，并使用原位RT-PCR在单个细胞的基础上证实。性类固醇丢失后IL-6受体表达增加的证明为为什么IL-6在性类固醇缺乏但不充足的状态下对骨骼稳态很重要提供了解释。
Both estrogen and androgen exert their antiosteoporotic effects, at least in part, by inhibiting IL-6 production, thereby suppressing osteoclastogenesis. Several observations, however, suggest that besides increased IL-6 production, sensitivity of the osteoclastogenic process to this cytokine is altered after ovariectomy. Based on this and evidence that the ligand-binding subunit of the IL-6 receptor (gp80) is a limiting factor for the actions of IL-6 on bone, are hypothesized that sex steroids regulate expression of the IL-6 receptor as well. We report that 17 beta-estradiol or dihydrotestosterone in vitro decreased the abundance of the gp80 mRNA as well as the mRNA of the signal-transducing subunit of the IL-6 receptor (gp130) in cells of the bone marrow stromal/osteoblastic lineage, and also decreased gp130 protein levels. These effects did not require new protein synthesis. In contrast to sex steroids, parathyroid hormone stimulated gp130 expression; this effect was opposed by sex steroids. Consistent with these findings, ovariectomy in mice caused an increase in expression of gp80, gp130, and IL-6 mRNAs in ex vivo bone marrow cell cultures as determined by quantitative reverse transcription (RT)-PCR, and confirmed on an individual cell basis using in situ RT-PCR. The demonstration of increased expression of the IL-6 receptor after loss of sex steroids provides an explanation for why IL-6 is important for skeletal homeostasis in the sex steroid-deficient, but not replete, state.