Jonathan A Young1, Elizabeth A Jensen2, Austin Stevens3, Silvana Duran-Ortiz1, Edward O List4, Darlene E Berryman5, John J Kopchick6. 1. Edison Biotechnology Institute, Ohio University, Athens, OH, United States of America; Molecular and Cellular Biology Program, Ohio University, Athens, OH, United States of America. 2. Edison Biotechnology Institute, Ohio University, Athens, OH, United States of America; Heritage College of Osteopathic Medicine, Athens, OH, United States of America; Translational Biomedical Sciences Program, Graduate College, Ohio University, Athens, OH, United States of America. 3. Edison Biotechnology Institute, Ohio University, Athens, OH, United States of America. 4. Edison Biotechnology Institute, Ohio University, Athens, OH, United States of America; Department of Specialty Medicine, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, United States of America. 5. Edison Biotechnology Institute, Ohio University, Athens, OH, United States of America; Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, United States of America; Diabetes Institute, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, United States of America. 6. Edison Biotechnology Institute, Ohio University, Athens, OH, United States of America; Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, United States of America. Electronic address: kopchick@ohio.edu.
Abstract
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.
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.
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