Effects of bovine growth hormone (GH) expression in transgenic mice on serum and pituitary immunoreactive mouse GH levels and pituitary GH-releasing factor binding sites.

A I Sotelo, A Bartke, D Turyn
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引用次数: 34

Abstract

Pituitary and serum levels of homologous growth hormone (GH) and characteristics of specific GH-releasing factor (GHRF) binding to pituitary homogenates were examined in transgenic mice expressing bovine GH (bGH) gene regulated by different promoters [mouse metallothionein-I (MT) or phosphoenolpyruvate carboxykinase (PEPCK)] and in their normal littermates. Pituitary GH concentration and GHRF binding were reduced by approximately 50% in transgenic MT-bGH mice in which serum bGH levels were about 20 micrograms/l and by approximately 95% in transgenic PEPCK-bGH mice in which serum bGH levels were tenfold higher. Suppression of plasma immunoreactive mouse GH (mGH) levels was detected in MT-bGH but not in PEPCK-bGH animals, presumably due to cross-reaction of the antiserum employed with bGH. Scatchard plots of GHRF binding to washed homogenates of pituitary glands from normal and young adult MT-bGH transgenic mice were curvilinear, indicating the presence of two types of binding sites, with low and high affinities. Both types of binding sites were reduced in number in MT-bGH transgenic mice without changes in their affinity. In 5-7-month-old MT-bGH transgenic mice there were changes in pituitary GH levels, in GHRF binding levels and in characteristics of GHRF binding that closely resembled the alterations described previously in aging rats. We conclude that over-expression of heterologous GH genes in transgenic mice can lead to partial or virtually complete suppression of somatotroph function, depending on the levels of heterologous GH in the circulation, and that transgenic MT-bGH mice exhibit symptoms of remarkably early onset of neuroendocrine aging.
牛生长激素(GH)转基因小鼠表达对血清和垂体免疫反应性小鼠GH水平及垂体GH释放因子结合位点的影响
在不同启动子[小鼠金属硫蛋白- 1 (MT)或磷酸烯醇丙酮酸羧激酶(PEPCK)]调控牛生长激素(bGH)基因的转基因小鼠及其正常窝鼠中,检测了垂体和血清中同源生长激素(GH)的水平以及垂体匀浆结合的特异性GH释放因子(GHRF)的特征。转基因MT-bGH小鼠的垂体GH浓度和GHRF结合降低了约50%,其中血清bGH水平约为20微克/升,转基因PEPCK-bGH小鼠的垂体GH浓度和GHRF结合降低了约95%,其中血清bGH水平高出10倍。在MT-bGH中检测到血浆免疫反应性小鼠GH (mGH)水平的抑制,而在PEPCK-bGH动物中则没有,可能是由于抗血清与bGH的交叉反应。正常和年轻成年MT-bGH转基因小鼠垂体洗净浆液中GHRF结合的Scatchard图呈曲线状,表明存在两种类型的结合位点,分别为低亲和力和高亲和力。在MT-bGH转基因小鼠中,这两种结合位点的数量都减少了,但它们的亲和力没有变化。在5-7个月大的MT-bGH转基因小鼠中,垂体GH水平、GHRF结合水平和GHRF结合特征的变化与先前在衰老大鼠中描述的变化非常相似。我们得出结论,转基因小鼠中外源生长激素基因的过度表达可导致部分或几乎完全抑制生长功能,这取决于循环中外源生长激素的水平,并且转基因MT-bGH小鼠表现出明显的早期神经内分泌衰老症状。
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