Objective

Growth hormone (GH) has been reported to enhance the intestinal barrier; as such, recombinant GH has been administered for several intestinal diseases. However, excess GH action has been implicated in increasing the risk of intestinal dysfunction. The goal of this study was to examine the direct effects of GH on the small and large intestines to clarify the role GH plays in intestinal function through the use of a mouse model.

Design

An intestinal epithelial-specific GH receptor (GHR) knockout (IntGHRKO) mouse line was generated using Cre-lox with the villin promoter driving Cre expression. The generated mice were characterized with respect to growth and intestinal phenotypes.

Results

IntGHRKO mice showed no significant changes in body length, weight, or composition compared to floxed controls. Male IntGHRKO mice had significantly shorter large intestines at 4 and 12 months of age. Intestinal barrier function was assessed by measuring the expression of tight junction related genes, as well as levels of serum endotoxin and fecal albumin. Results showed sex differences as males had an increase in occludin levels but normal serum endotoxin and fecal albumin; while, females had changes in fecal albumin levels with normal occludin and serum endotoxin. Evaluation of glucose tolerance and fat absorption also showed sex differences as females were glucose intolerant, while males had impaired fat absorption. Histopathology revealed a trend towards decreased villus height in males, which could explain the sex difference in glucose homeostasis.

Conclusions

Overall, the data demonstrate that disruption of GH on the intestinal epithelial cells modestly affects the intestinal gross anatomy, morphology, and function in a sex-specific manner.

中文翻译：

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肠道特异性GH受体敲除（IntGHRKO）小鼠的特征。

目的

据报道，生长激素（GH）可以增强肠道屏障。因此，已将重组GH用于几种肠道疾病。但是，过量的GH作用与增加肠道功能障碍的风险有关。这项研究的目的是检验GH对小肠和大肠的直接作用，以阐明GH通过使用小鼠模型在肠功能中的作用。

设计

肠道上皮特异性GH受体（GHR）敲除（IntGHRKO）小鼠系使用Cre-lox和villin启动子驱动Cre表达产生。就生长和肠表型表征所产生的小鼠。

结果

与亚麻对照相比，IntGHRKO小鼠的体长，体重或组成无明显变化。雄性IntGHRKO小鼠在4和12个月大时，大肠明显较短。通过测量紧密连接相关基因的表达以及血清内毒素和粪便白蛋白的水平来评估肠屏障功能。结果显示性别差异，因为男性的闭合素水平升高，但血清内毒素和粪便白蛋白却正常；而女性的粪便白蛋白水平随着正常的闭合素和血清内毒素而改变。对葡萄糖耐量和脂肪吸收的评估也显示出性别差异，因为女性不耐葡萄糖，而男性脂肪吸收受损。组织病理学揭示了男性绒毛高度降低的趋势，

结论

总体而言，数据表明对肠上皮细胞的GH破坏以性别特异性方式适度影响肠的总体解剖结构，形态和功能。