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Physiol. Rev. 78: 1193-1231, 1998;
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PHYSIOLOGICAL REVIEWS   Vol. 78 No. 4 October 1998, pp. 1193-1231
Copyright ©1998 The American Physiological Society

Current Understanding of the Molecular Actions of Vitamin D

GLENVILLE JONES, STEPHEN A. STRUGNELL, AND HECTOR F. DeLUCA

Departments of Biochemistry and Medicine, Queen's University, Kingston, Ontario, Canada; and Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin

Jones, Glenville, Stephen A. Strugnell, and Hector F. DeLuca. Current Understanding of the Molecular Actions of Vitamin D. Physiol. Rev. 78: 1193-1231, 1998. --- The important reactions that occur to the vitamin D molecule and the important reactions involved in the expression of the final active form of vitamin D are reviewed in a critical manner. After an overview of the metabolism of vitamin D to its active form and to its metabolic degradation products, the molecular understanding of the 1alpha -hydroxylation reaction and the 24-hydroxylation reaction of the vitamin D hormone is presented. Furthermore, the role of vitamin D in maintenance of serum calcium is reviewed at the physiological level and at the molecular level whenever possible. Of particular importance is the regulation of the parathyroid gland by the vitamin D hormone. A third section describes the known molecular events involved in the action of 1alpha ,25-dihydroxyvitamin D3 on its target cells. This includes reviewing what is now known concerning the overall mechanism of transcriptional regulation by vitamin D. It describes the vitamin D receptors that have been cloned and identified and describes the coactivators and retinoid X receptors required for the function of vitamin D in its genomic actions. The presence of receptor in previously uncharted target organs of vitamin D action has led to a study of the possible function of vitamin D in these organs. A good example of a new function described for 1alpha ,25-dihydroxyvitamin D3 is that found in the parathyroid gland. This is also true for the role of vitamin D hormone in skin, the immune system, a possible role in the pancreas, i.e., in the islet cells, and a possible role in female reproduction. This review also raises the intriguing question of whether vitamin D plays an important role in embryonic development, since vitamin D deficiency does not prohibit development, nor does vitamin D receptor knockout. The final section reviews some interesting analogs of the vitamin D hormone and their possible uses. The review ends with possible ideas with regard to future directions of vitamin D drug design.




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