School of Allied Health Sciences, Medical College of Georgia, Augusta, GA 30912, USA.
Am J Physiol Regul Integr Comp Physiol. 2010 Mar;298(3):R790-8. doi: 10.1152/ajpregu.00728.2009. Epub 2009 Dec 30.
Recent studies have indicated that follicle-stimulating hormone (FSH) promotes bone loss. The present study tested the hypothesis that FSH enhances the activity of bone-resorbing cytokines [interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, and IL-6], either by inducing their secretion or by altering their receptor expression. Thirty-six women between the ages of 20 and 50 were assessed for bone mineral density (BMD), reproductive hormone, cytokine ligand and soluble receptor concentrations, and surface expression of cytokine receptors on monocytes. In addition, isolated mononuclear cells were incubated in vitro with exogenous FSH. Univariate regression analyses indicated that BMD was inversely related to serum FSH (r = -0.29 to -0.51, P = 0.03-0.001, depending upon the skeletal site). Physical activity and body composition were also identified as significant factors by multiple regressions. Exogenous FSH induced isolated cells to secrete IL-1beta, TNF-alpha, and IL-6 in proportion to the surface expression of FSH receptors on the monocytes. Endogenous (serum) FSH concentrations correlated with the circulating concentrations of these cytokines. None of these individual cytokines was related to BMD, but the IL-1beta to IL-1 receptor antagonist (IL-1Ra) ratio was inversely related to BMD (r = -0.53, P = 0.002) in all but the most physically active women, who had significantly lower expression of IL-1 type I receptors relative to type II (decoy receptors, P = 0.01). Physical activity also correlated positively with secretion of inhibitory soluble IL-1 receptors (r = 0.53, P = 0.003). Moreover, IL-1Ra correlated strongly with percent body fat (r = 0.66, P < 0.0001). These results indicate that BMD is related to FSH concentration, physical activity, and body composition. Although each of these factors likely has direct effects on bone, the present study suggests that each may also influence BMD by modulating the activity of the osteoresorptive cytokine IL-1beta.
最近的研究表明，卵泡刺激素（FSH）可促进骨质流失。本研究通过检测 FSH 对破骨细胞因子（IL-1β、TNF-α和 IL-6）活性的影响，验证了其促进骨质流失的假说，该影响既可以通过诱导这些因子的分泌，也可以通过改变它们的受体表达来实现。我们评估了 36 名年龄在 20 至 50 岁之间的女性的骨矿物质密度（BMD）、生殖激素、细胞因子配体和可溶性受体浓度，以及单核细胞表面细胞因子受体的表达。此外，我们还将分离的单核细胞在体外与外源性 FSH 孵育。单变量回归分析表明，BMD 与血清 FSH 呈负相关（r = -0.29 至 -0.51，P = 0.03-0.001，取决于骨骼部位）。身体活动和身体成分也是通过多元回归确定的重要因素。外源性 FSH 诱导分离细胞分泌 IL-1β、TNF-α和 IL-6，其比例与单核细胞表面 FSH 受体的表达成正比。内源性（血清）FSH 浓度与这些细胞因子的循环浓度相关。这些细胞因子中没有一个与 BMD 相关，但除了身体活动最活跃的女性外，IL-1β与 IL-1 受体拮抗剂（IL-1Ra）的比值与 BMD 呈负相关（r = -0.53，P = 0.002），这些女性的 I 型 IL-1 受体的表达相对 II 型（诱饵受体）显著降低（P = 0.01）。身体活动也与抑制性可溶性 IL-1 受体的分泌呈正相关（r = 0.53，P = 0.003）。此外，IL-1Ra 与体脂百分比密切相关（r = 0.66，P <0.0001）。这些结果表明，BMD 与 FSH 浓度、身体活动和身体成分有关。虽然这些因素都可能直接影响骨骼，但本研究表明，它们还可以通过调节破骨细胞因子 IL-1β 的活性来影响 BMD。
