view in publisher's site

Vitamin D and Human Health: Lessons from Vitamin D Receptor Null Mice

Abstract The vitamin D endocrine system is essential for calcium and bone homeostasis. The precise mode of action and the full spectrum of activities of the vitamin D hormone, 1,25-dihydroxyvitamin D [1,25-(OH)2D], can now be better evaluated by critical analysis of mice with engineered deletion of the vitamin D receptor (VDR). Absence of a functional VDR or the key activating enzyme, 25-OHD-1α-hydroxylase (CYP27B1), in mice creates a bone and growth plate phenotype that mimics humans with the same congenital disease or severe vitamin D deficiency. The intestine is the key target for the VDR because high calcium intake, or selective VDR rescue in the intestine, restores a normal bone and growth plate phenotype. The VDR is nearly ubiquitously expressed, and almost all cells respond to 1,25-(OH)2D exposure; about 3% of the mouse or human genome is regulated, directly and/or indirectly, by the vitamin D endocrine system, suggesting a more widespread function. VDR-deficient mice, but not vitamin D- or 1α-hydroxylase-deficient mice, and man develop total alopecia, indicating that the function of the VDR and its ligand is not fully overlapping. The immune system of VDR- or vitamin D-deficient mice is grossly normal but shows increased sensitivity to autoimmune diseases such as inflammatory bowel disease or type 1 diabetes after exposure to predisposing factors. VDR-deficient mice do not have a spontaneous increase in cancer but are more prone to oncogene- or chemocarcinogen-induced tumors. They also develop high renin hypertension, cardiac hypertrophy, and increased thrombogenicity. Vitamin D deficiency in humans is associated with increased prevalence of diseases, as predicted by the VDR null phenotype. Prospective vitamin D supplementation studies with multiple noncalcemic endpoints are needed to define the benefits of an optimal vitamin D status.

ویتامین D و سلامت انسان: درس‌هایی از ویتامین D Receptor Null

ترجمه شده با


پر ارجاع‌ترین مقالات مرتبط:

  • مقاله Endocrinology
  • ترجمه مقاله Endocrinology
  • مقاله درون‌ریزشناسی
  • ترجمه مقاله درون‌ریزشناسی
  • مقاله Endocrinology, Diabetes and Metabolism
  • ترجمه مقاله Endocrinology, Diabetes and Metabolism
  • مقاله درون‌ریزشناسی، دیابت و متابولیسم
  • ترجمه مقاله درون‌ریزشناسی، دیابت و متابولیسم
سفارش ترجمه مقاله و کتاب - شروع کنید

95/12/18 - با استفاده از افزونه دانلود فایرفاکس و کروم٬ چکیده مقالات به صورت خودکار تشخیص داده شده و دکمه دانلود فری‌پیپر در صفحه چکیده نمایش داده می شود.