van Buul-Offers S C, Reijnen-Gresnigt M G, Hoogerbrugge C M, Bloemen R J, Kuper C F, Van den Brande J L
Department of Pediatrics, Wilhelmina Children's Hospital, University of Utrecht, The Netherlands.
Endocrinology. 1994 Sep;135(3):977-85. doi: 10.1210/endo.135.3.7520865.
The actions and interactions of recombinant insulin-like growth factor-I and -II (IGF-I and IGF-II), alone or in combination with human GH on body growth and the growth of several organs were studied in the Snell dwarf mouse. IGF-I and -II stimulate to a similar extent sulfate incorporation into cartilage, and both IGFs increase body length and weight. IGF-II as well as IGF-I have clear effects on the size of the submandibular salivary glands, kidneys, and spleen. IGF-II, however, did not influence the weight of the lung, in contrast with IGF-I. GH treatment alone resulted in growth of the liver, whereas both IGFs were inactive. Surprisingly, IGF-II and, to a lesser extent, IGF-I inhibited GH-induced growth of the liver. Glycogen storage in the liver was decreased by treatment with IGF-II alone or in combination with GH, as shown by histological examination. It was not affected by GH, IGF-I, or GH plus IGF-I. Also, the size of the centrilobular hepatocytes was decreased by treatment with IGF-II and IGF-II plus GH; GH alone had a hypertrophic effect, whereas IGF-I or GH plus IGF-I had none. In contrast to GH, IGFs did not increase polyploidy. Treatment with IGF-II increased the level of IGFBP-3, as did IGF-I or GH treatment, as shown by Western ligand blotting. The IGFs appeared to have a greater effect on the induction of 38.5-kilodalton IGFBP-3 than GH, suggesting a different role in the regulation of glycosylation. In conclusion, IGF-I and IGF-II as well as GH have a stimulatory effect on general body growth and are effective in the stimulation of serum IGFBP-3, sulfate incorporation into cartilage, as well as the growth of specific organs in Snell dwarf mice. Both IGFs, alone or in combination with GH, show distinct effects on the growth of the liver with respect to several histological parameters, which require further exploration.
在斯内尔侏儒小鼠中研究了重组胰岛素样生长因子-I和-II（IGF-I和IGF-II）单独或与人生长激素（GH）联合对身体生长及多个器官生长的作用和相互作用。IGF-I和-II刺激硫酸根掺入软骨的程度相似，且两种IGF均增加体长和体重。IGF-II以及IGF-I对颌下唾液腺、肾脏和脾脏的大小有明显影响。然而，与IGF-I相反，IGF-II不影响肺的重量。单独使用GH治疗可导致肝脏生长，而两种IGF均无活性。令人惊讶的是，IGF-II以及在较小程度上IGF-I抑制GH诱导的肝脏生长。组织学检查显示，单独使用IGF-II或与GH联合治疗可降低肝脏中的糖原储存。它不受GH、IGF-I或GH加IGF-I的影响。此外，用IGF-II和IGF-II加GH治疗可使中央小叶肝细胞的大小减小；单独使用GH有肥大作用，而IGF-I或GH加IGF-I则无此作用。与GH相反，IGF不增加多倍体。Western配体印迹法显示，与IGF-I或GH治疗一样，用IGF-II治疗可增加IGFBP-3的水平。IGF似乎比GH对38.5千道尔顿IGFBP-3的诱导作用更大，表明在糖基化调节中起不同作用。总之，IGF-I和IGF-II以及GH对整体身体生长有刺激作用，并且在刺激血清IGFBP-3、硫酸根掺入软骨以及斯内尔侏儒小鼠特定器官的生长方面有效。两种IGF单独或与GH联合，在肝脏生长的几个组织学参数方面显示出不同的作用，这需要进一步探索。
