Distinct Effects of Growth Hormone and Glutamine on Activation of Intestinal Stem Cells

Background: For patients with short bowel syndrome under parenteral nutrition support, growth hormone (GH) and glutamine (GLN) have been found to help the growth of intestinal mucosa. In this research, we studied the effects of GH and GLN on intestinal stem cells (ISCs). Methods: The in vitro and in vivo effects of GH and/or GLN on ISCs were evaluated by observing the ability of ISCs to form organoids in a Matrigel culture system. The expression levels of stemness and differentiation markers in ISCs and organoids were assessed using quantitative real-time polymerase chain reaction, immunofluorescence assay, and immunohistochemistry staining. Results: In vitro administration of GH activated the stemness of ISCs, whereas GLN enhanced the expression of chromogranin A and Muc2, which are differentiation markers in enteroendocrine and goblet cells, respectively. Administration of GH or GLN in mice showed that GH, but not GLN, upregulated the proliferative activity of ISCs with increased formation of crypt organoids. In addition, GH increased the expression of Lgr5 and GLN enhanced expression of Muc2 in the crypt fractions of the intestines in mice. Conclusion: These results suggest that GH mainly enhances proliferative activities, whereas GLN promotes the differentiation potential of ISCs.