Abstract
Purpose
Growth hormone (GH) has an important role in intestinal barrier function, and abnormalities in GH action have been associated with intestinal complications. Yet, the impact of altered GH on intestinal gross anatomy and morphology remains unclear.
Methods
This study investigated the influence of GH signaling on gross anatomy, morphology, and fibrosis by characterizing the small and large intestines in male and female bovine growth hormone transgenic (bGH) mice and GH receptor gene-disrupted (GHR−/−) mice at multiple timepoints.
Results
The length, weight, and circumference of the small and large intestines were increased in bGH mice and decreased in GHR−/− mice across all ages. Colon circumference was significantly increased in bGH mice in a sex-dependent manner while significantly decreased in male GHR−/− mice. Villus height, crypt depth, and muscle thickness of the small intestine were generally increased in bGH mice and decreased in GHR−/− mice compared to controls with age- and sex-dependent exceptions. Colonic crypt depth and muscle thickness in bGH and GHR−/− mice were significantly altered in an age- and sex-dependent manner. Fibrosis was increased in the small intestine of bGH males at 4 months of age, but no significant differences were seen between genotypes at other timepoints.
Conclusion
This study observed notable opposing findings in the intestinal phenotype between mouse lines with GH action positively associated with intestinal gross anatomy (i.e. length, weight, and circumference). Moreover, GH action appears to alter morphology of the small and large intestines in an age- and sex-dependent manner.
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Data availability
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Code availability
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Abbreviations
- bGH:
-
Bovine growth hormone transgenic mice
- GHR−/−:
-
Growth hormone receptor gene disrupted mice
- SI:
-
Small intestines
- LI:
-
Large intestines
- IBD:
-
Inflammatory bowel disease
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Acknowledgements
We would like to thank Julie Buckley and the Ohio University Histology Core for assistance in preparing and staining intestinal sections. We would also like to thank Alison Brittain for tissue samples at 6 weeks of age, Stephen Bell for his assistance in the dissection and adipose tissue extraction of the bGH mice and controls at all timepoints, Silvana Duran for her assistance toward tissue and body weight measurements for GHR−/− mice at 13 months of age, and Zachary Jackson for his assistance in preparing intestinal samples at 6 and 11 months of age.
Funding
This work was supported in part by NIH grant #AG059779, Ohio University Heritage College of Osteopathic Medicine, The Diabetes Institute at Ohio University, and the State of Ohio’s Eminent Scholar Program that includes a gift from Milton and Lawrence Goll. This study was partially funded by the John J. Kopchick Molecular and Cellular Biology/Translational Biomedical Sciences Research Fellowship and a fellowship from Osteopathic Heritage Foundations at Ohio University Heritage College of Osteopathic Medicine.
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EJ, EL, JK, and DB contributed to the study conception and design. Material preparation, data collection and analysis were performed by EJ, JY, JK, MO, and JB. The manuscript was written by EJ and JY, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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Jensen, E.A., Young, J.A., Kuhn, J. et al. Growth hormone alters gross anatomy and morphology of the small and large intestines in age- and sex-dependent manners. Pituitary 25, 116–130 (2022). https://doi.org/10.1007/s11102-021-01179-8
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DOI: https://doi.org/10.1007/s11102-021-01179-8