Mark D DeBoer1, Yongli Li, Steven Cohn. 1. Division of Pediatric Endocrinology, Department of Pediatrics, University of Virginia, P.O. Box 800386, Charlottesville, VA 22908, USA. deboer@virginia.edu
Abstract
BACKGROUND: Inflammatory bowel disease that begins prior to puberty frequently causes a delay in puberty resulting in losses of growth, bone mineralization, and self esteem. A major cause of this pubertal delay is likely due in part to the effect of decreased levels of leptin on the function of the hypothalamic-pituitary-gonadal axis, though systemic inflammation is also thought to play a role. METHODS: To investigate further whether low leptin levels alone were responsible for delayed puberty in colitis, we induced colitis in 23-day-old female mice using 3% dextran sodium sulfate (DSS), resulting in 10 days of worsening colitis. These mice were compared to controls that were free-feeding and food-restricted (FR) mice that were given only enough food to keep them the same weight as the DSS group. All groups were followed for the timing of vaginal opening until 33 days old, when they were euthanized and their serum collected. RESULTS: DSS-treated mice exhibited later timing of vaginal opening relative to both of the other groups, as well as increased colonic inflammation by cytology and increased serum levels of interleukin (IL)-6 and tumor necrosis factor(TNF)-alpha. The difference in the timing of vaginal opening between the DSS and FR groups occurred despite equivalent serum levels of leptin between the groups and despite an increase in corticosterone in the FR group relative to both of the other groups. CONCLUSIONS: We conclude that DSS colitis causes delay in puberty in sexually immature mice beyond what would be expected from decreases in weight and leptin levels.
BACKGROUND:Inflammatory bowel disease that begins prior to puberty frequently causes a delay in puberty resulting in losses of growth, bone mineralization, and self esteem. A major cause of this pubertal delay is likely due in part to the effect of decreased levels of leptin on the function of the hypothalamic-pituitary-gonadal axis, though systemic inflammation is also thought to play a role. METHODS: To investigate further whether low leptin levels alone were responsible for delayed puberty in colitis, we induced colitis in 23-day-old female mice using 3% dextran sodium sulfate (DSS), resulting in 10 days of worsening colitis. These mice were compared to controls that were free-feeding and food-restricted (FR) mice that were given only enough food to keep them the same weight as the DSS group. All groups were followed for the timing of vaginal opening until 33 days old, when they were euthanized and their serum collected. RESULTS:DSS-treated mice exhibited later timing of vaginal opening relative to both of the other groups, as well as increased colonic inflammation by cytology and increased serum levels of interleukin (IL)-6 and tumor necrosis factor(TNF)-alpha. The difference in the timing of vaginal opening between the DSS and FR groups occurred despite equivalent serum levels of leptin between the groups and despite an increase in corticosterone in the FR group relative to both of the other groups. CONCLUSIONS: We conclude that DSS colitis causes delay in puberty in sexually immature mice beyond what would be expected from decreases in weight and leptin levels.
Authors: Mark D DeBoer; Barrett H Barnes; Nicholas A Stygles; James L Sutphen; Stephen M Borowitz Journal: J Pediatr Gastroenterol Nutr Date: 2012-04 Impact factor: 2.839
Authors: Mark D DeBoer; Meena Thayu; Lindsay M Griffin; Robert N Baldassano; Lee A Denson; Babette S Zemel; Michelle R Denburg; Hannah E Agard; Rita Herskovitz; Jin Long; Mary B Leonard Journal: J Pediatr Date: 2016-02-09 Impact factor: 4.406
Authors: Christina Corre; Gen Shinoda; Hao Zhu; Diana L Cousminer; Christine Crossman; Christian Bellissimo; Anna Goldenberg; George Q Daley; Mark R Palmert Journal: J Endocrinol Date: 2015-12-23 Impact factor: 4.286
Authors: Mark D DeBoer; Vidhya Vijayakumar; Meiqing Gong; John L Fowlkes; Rachel M Smith; Fernando Ruiz-Perez; James P Nataro Journal: Nutr Res Date: 2017-02-07 Impact factor: 3.315