MON-479 Gross and Microscopic Intestinal Morphology of Bovine Growth Hormone Transgenic Mice Longitudinally

Abstract

Growth hormone (GH) has been shown to have important effects on the intestines, demonstrated by its use in treatment of short bowel syndrome and the increase in colon polyps seen in acromegaly. Accordingly, GH has been shown to affect intestinal morphology at the gross and microscopic levels, including increased intestinal length and increased villus height in situations of excess GH aged 2 months. However, the effect of excess GH on intestinal morphology longitudinally or at advanced ages has not been extensively examined. This study measured the gross and microscopic intestinal morphology at multiple ages in bovine GH (bGH) transgenic mice, a mouse model of acromegaly. Adult bGH mice and littermate controls aged 6, 11, or 13 months were used for this study. The intestines were dissected, mesenteric fat was removed, and the small intestine (SI) was separated from the large intestine (LI). The length and circumference of the SI and the LI were measured. Intestinal portions were processed using the Swiss roll method, paraffin embedded, sectioned, and stained. The images of the sections were then used to measure the villus height, crypt depth and muscle thickness. In accordance with previous reports in humans and mice, chronic GH excess causes increased intestinal length. This difference was present in both the SI and LI and at 6, 11, and 13 months of age. bGH mice at all three ages had increased SI weight. LI weight was increased in bGH mice at 6 and 13 months of age, but there was no increase at 11 months of age. At 13 months of age, the LI circumference was increased in bGH mice, and the SI circumference at 6 months of age was also increased. At the microscopic level, the 6-month-old bGH mice had significantly increased crypt depth in the duodenum and jejunum, and a trend in the ileum. There is also a trend towards increased villus height in the 6-month bGH mice in all three sections of the SI that did not reach significance. The only change observed in the 11-month bGH mice was increased muscle thickness in the duodenum. The results of this study indicate that chronic GH excess indeed increases intestinal length, a change that persists longitudinally. The previously reported increase in intestinal villus height in response to GH excess was not observed in this experiment, but increased crypt depth was observed in the youngest cohort. The oldest group had an increase in SI circumference that coincided with increased muscle thickness in the 11-month bGH mice. In summary, our data show a potent trophic effect of GH on the intestinal tract, as well as an effect on the microscopic morphology of the intestines; however, the microscopic changes differ from those previously reported and do not seem to persist over the lifespan of a mouse. Acknowledgements: This work was supported by the State of Ohio’s Eminent Scholar Program that includes a gift from Milton and Lawrence Goll, by AMVETS, and by the Diabetes Institute at Ohio University