Dysregulation of the Vitamin D Nuclear Receptor May Contribute to the Higher Prevalence of Some Autoimmune Diseases in Women
Researchers have noted that the incidence of autoimmune diseases, such as Hashimoto's thyroiditis, is markedly higher in women than in men, but to date the reason for this disparity has been unclear. The vitamin D nuclear receptor (VDR) is expressed in the human cycling endometrium. Because the...
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Published in | Annals of the New York Academy of Sciences Vol. 1173; no. 1; pp. 252 - 259 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
Malden, USA
Blackwell Publishing Inc
01.09.2009
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Subjects | |
Online Access | Get full text |
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Summary: | Researchers have noted that the incidence of autoimmune diseases, such as Hashimoto's thyroiditis, is markedly higher in women than in men, but to date the reason for this disparity has been unclear. The vitamin D nuclear receptor (VDR) is expressed in the human cycling endometrium. Because the VDR controls expression of the cathelicidin and β‐defensin antimicrobial peptides (AmPs), dysregulation of the receptor greatly compromises the innate immune response. Increasing evidence indicates the presence of a chronic, intraphagocytic, metagenomic microbiota in patients with autoimmune disease that may survive by dysregulating the VDR. VDR dysregulation, in turn, prevents the breakdown of the active vitamin D metabolite 1,25‐hydroxyvitamin D (1,25‐D) by CYP24. In silico data suggest that when 1,25‐D rises above its normal range, it binds the α/β thyroid receptors, the glucocorticoid receptor (GCR), and the androgen receptor (AR), displacing their native ligands and causing an array of hormonal imbalances. If T3 is displaced from α‐thyroid, thyroiditis may result. Because the VDR, GCR, and AR also express multiple families of AmPs, expression of these natural antibiotics further wanes in response to dysregulation by 1,25‐D. The end result is a system‐wide drop in AmP expression that may allow pathogens to spread with greater ease. Because women have an extra site of VDR expression in the endometrium, the drop in AmP expression associated with nuclear receptor dysregulation may disproportionately affect them. This would cause women to accumulate higher bacterial loads than their male counterparts, particularly during early pregnancy when 1,25‐D levels rise by 40%. |
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Bibliography: | ArticleID:NYAS4672 ark:/67375/WNG-PG4W02S2-R istex:EA7FCC14DF40598A69443E75B2B6341D1C0EA4BB ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1 |
ISSN: | 0077-8923 1749-6632 |
DOI: | 10.1111/j.1749-6632.2009.04672.x |