The chemical identification and chemical synthesis of vitamin D earned A. Rickets, as a disease of children of either rich families (deliberately avoiding exposure to sunshine in countries such as the United Kingdom and India) or very poor families living in the slums of big European industrialized cities, gradually disappeared thereafter due either to better exposure to sunshine or to the oral use of vitamin D-rich cod liver oil. Steenbock discovered, around the same time, that UV irradiation of vegetarian oil produced the antirachitic substance vitamin D 2 and patented this discovery. The origin of the disease was largely unknown until the discovery of the dual origin of vitamin D at the beginning of the 20th century as a nutritional compound by Mellanby in the United Kingdom and McCollum in the United States (discovery of dietary vitamin D), whereas Huldshinsky, Chick, and Hume, Hess, and Weinstock discovered the curative effects of UV light ( 3, 4, 5, 6, 7, 8). In addition, a Dutch physician who also lived briefly in London, Ireland, and Paris published in 1649, in his native language, a description of “tabes pectoralis”, the typical thoracic malformation of rickets ( 1, 2). thesis equivalent presented at the University of Lugdunum Batavorum (Leiden, The Low Countries) in 1645 by Daniel Whistler and, briefly thereafter, by Francis Glisson (in collaboration with G. The first extensive description of the clinical picture of rickets, including the name, dates from the 17th century in a Ph.D. History of the vitamin D endocrine system Prospective vitamin D supplementation studies with multiple noncalcemic endpoints are needed to define the benefits of an optimal vitamin D status.Ī. Vitamin D deficiency in humans is associated with increased prevalence of diseases, as predicted by the VDR null phenotype. They also develop high renin hypertension, cardiac hypertrophy, and increased thrombogenicity. VDR-deficient mice do not have a spontaneous increase in cancer but are more prone to oncogene- or chemocarcinogen-induced tumors. 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, 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 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.
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. 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 ASCENT ANABOLIC EXPRESS FULL
The precise mode of action and the full spectrum of activities of the vitamin D hormone, 1,25-dihydroxyvitamin D, can now be better evaluated by critical analysis of mice with engineered deletion of the vitamin D receptor (VDR). The vitamin D endocrine system is essential for calcium and bone homeostasis.
0 kommentar(er)
