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Title: Sex difference in resistance to Dexamethasone-induced apoptosis in NOD mice: treatment with 1,25(OH)2D3 restores defect
Authors: Casteels, Kristina
Gysemans, Conny
Waer, Mark
Bouillon, Roger
Laureys, Jozef
Depovere, Jos
Mathieu, Chantal # ×
Issue Date: Jul-1998
Series Title: Diabetes vol:47 issue:7 pages:1033-7
Abstract: The NOD mouse, a model for type 1 diabetes, is characterized by resistance to apoptosis in immunocytes. The aim of this study was to investigate a link between apoptosis in NOD thymocytes and autoimmunity. First, we demonstrated that the sexual dimorphism in diabetes incidence in NOD mice (females are more diabetes-prone than males) is reflected by differences in apoptosis. Apoptosis in NOD thymocytes, 24 h after dexamethasone, was decreased in both sexes compared with C57B1/6, but it was lower in female mice (26 +/- 2%) than in male mice (50 +/- 3%, P < 0.001). Further, we demonstrated that sex hormones themselves play a central role in this difference, since castration of NOD male mice, which increases diabetes incidence, decreased apoptosis levels (32 +/- 2%), while treatment of NOD female mice with dihydrotestosterone, which protects against diabetes, restored apoptosis to male levels (42 +/- 1.5%). Finally, we demonstrated that 1,25-dihydroxyvitamin D3, a steroid hormone that prevents diabetes in NOD mice, restored apoptosis levels to C57B1/6 reference levels. This improved apoptosis was seen in male (68 +/- 1 vs. 50 +/- 3% in untreated NOD mice, P < 0.001) but especially in female NOD mice (51 +/- 5 vs. 26 +/- 2% in untreated NOD mice, P < 0.001). Fluorescence-activated cell sorter analysis of thymocyte subsets revealed marked differences, especially in CD4+CD8+ and CD4+ cells. We conclude that the sexual dimorphism in diabetes incidence in NOD mice is paralleled by a dimorphism in resistance to apoptotic signals in NOD thymocytes. This resistance to apoptosis is driven by sex hormones and is corrected by 1,25-dihydroxyvitamin D3.
URI: 
ISSN: 0012-1797
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Medical Clerkships Centers
Laboratory of Nephrology
Clinical and Experimental Endocrinology
Laboratory of Experimental Transplantation
× corresponding author
# (joint) last author

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