HORMONES AND AGING--PITUITARY-HYPOTHALAMIC FUNCTION IN EXPERIMENTAL ANIMALS

在一项关于年龄对组织对激素反应的影响的研究中， 年轻和老年雄性小鼠分别接受重组人生长激素、生长激素、生长激素加T或安慰剂治疗。 从不同的组织中提取mRNA，并通过 Northern印迹、RNA酶保护试验或模板特异性 定量聚合酶链式反应检测胰岛素样生长因子-I、胰岛素样生长因子-I受体、 胰岛素样生长因子-I结合蛋白1和3，延伸因子L-α以及 组织特异性分化因子和结构蛋白(例如 肌肉、肌生成素和α-肌球蛋白重链；在骨骼α-1 前胶原蛋白)。治疗前，老年患者IGF-I水平显著降低 小鼠血浆T和EF-1α/18S m RNA比值降低，但 不是很明显。经重组人生长激素治疗后，IGF-I水平趋于 增加，但这仅在5天后的老年小鼠中显著。在10点之后 D，单独应用重组生长激素使EF-1α/18SmRNA比值升高 在成熟和老年小鼠中也是如此，而单独使用T的治疗增加了 EF-1α/18S mRNA仅在老年小鼠中表达。重组人生长激素+T细胞联合治疗 成年小鼠5天后EF-1α/18S m RNA显著升高。 这些数据表明，在雄性小鼠中，EF-1α基因的表达可以 由GH或T增加，但对GH+T没有相加反应 似乎影响了这种反应的模式。这项工作的继续 应包括Western对IGF-I和IGF-I受体蛋白的估计 印迹和核径流分析以确定是否增加 在EF-1α中观察到的表达代表转录水平的调节。

In an investigation of the effects of age on tissue responses to hormones, young and old male mice were treated with rhGH, T, GH plus T, or placebo and mRNA extracts were prepared from various tissues and probed by Northern blotting, RNA'ase protection assay, or template specific quantitative PCR to quantify specific mRNA's for IGF-I,IGF-I receptor, IGF-I binding proteins 1 and 3, and elongation factor l-alpha as well as tissue specific differentiation factors and structural proteins (e.g. in muscle, myogenin and alpha-myosin heavy chain; in bone alpha- 1 procollagen). Pretreatment, IGF-I levels were significantly lower in old mice, and plasma T and the ratio of EF-1alpha/18S mRNA were reduced, but not significantly so. After rhGH treatment, IGF-I levels tended to increase, but this was significant only in old mice after 5 days. After 10 days, treatment with rhGH alone increased the ratio of EF-1alpha/18SmRNA similarly in mature and old mice, whereas treatment with T alone increased EF-1alpha/18S mRNA only in old mice. Combination treatment with rhGH + T increased EF-1alpha/l8S mRNA significantly after 5days in mature mice. These data suggest that, in male mice, EF-1alpha gene expression can be increased by GH or T, but with no additive response to GH + T. Aging appears to affect the pattern of this response. Continuation of this work should include estimation of IGF-I and IGF-I receptor protein by Western blotting and nuclear run-off assays to establish whether the increases observed in EF-1alpha represent regulation at the transcriptional level.