SUN-LB51 Growth Hormone Deficiency and Resistance Result in Altered Intestinal Gross Anatomy and Morphology in Mice at Adult and Older Adult Timepoints

Abstract

Growth hormone (GH) plays an important role in sustaining intestinal integrity. That is, GH has been shown to decrease intestinal permeability and bacterial translocation and alter gut functions like macronutrient absorption and immune function. To date, however, few studies have investigated how GH action – especially global knockdown of GH action - alters intestinal gross anatomy and morphology. This study characterized the intestinal gross anatomy and morphology of two mouse lines with decreased GH action (with improved health-span and insulin sensitivity): 1) GH gene disrupted (GH-/-) mice (GH deficiency) and 2) GH receptor knockout (GHR-/-) mice (GH resistance). Intestines from GH-/- and GHR-/- mice and their respective littermate controls at adult (12-13 mo.) and older adult (19 mo. and 24 mo., respectively) were used for this study. Both length and weight of small and large intestines were measured at the time of dissection. Six sections for the small intestine and four sections for the large intestine were prepared using a swill roll technique. Images were taken at 100x magnification with a Nikon Eclipse E600 microscope, and villus height, crypt depth, and muscle thickness were measured using ImageJ. All measurements were analyzed using Student t-test, and Cohen’s d effect size was used to compare the intestinal phenotype between lines. Both GHR-/- and GH-/- displayed altered intestinal gross anatomy and morphology. GHR-/- mice at 13 mo. of age had significantly shorter small and large intestines compared to controls. Morphologically, GHR-/- mice also showed significantly decreased villus height in the duodenum and decreased villus height and crypt depth in the jejunum. Likewise, GHR-/- mice at 24 mo. of age had significantly decreased intestinal length, and circumference in both small and large intestines with significantly decreased crypt depth in the ileum. Similar to GHR-/- mice, GH-/- mice at both 12 mo. and 19 mo. of age exhibited significantly shorter small and large intestines compared to controls with significantly smaller circumferences. Duodenum and jejunum of GH-/- mice also had a significant decrease in villus height in the duodenum and jejunum. In this study, decreased GH action is apparent in significantly affecting intestinal morphology and gross anatomy. GHR-/- and GH-/- mice had similar changes in gross anatomy (i.e. length and circumference) and villus height of the duodenum and jejunum. Similar changes to intestinal gross anatomy and morphology were also seen across the different ages in the mice. These findings suggest that decreased GH action influences the gross anatomy of both small and large intestines, and yet has a distinctive section-dependent impact on intestinal morphology. Research needs to be conducted to understand how these structural changes relate to gut function and assess intestinal phenotype at a younger ages in these mouse lines.