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Current understanding of the molecular actions of vitamin D Jones G; Strugnell SA; DeLuca HFPhysiol Rev 1998[Oct]; 78 (4): 1193-231The 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.|Amino Acid Sequence[MESH]|Animals[MESH]|Calcitonin/physiology[MESH]|Calcium/physiology[MESH]|Drug Design[MESH]|Humans[MESH]|Hydroxylation[MESH]|Molecular Sequence Data[MESH]|Parathyroid Glands/physiology[MESH]|Receptors, Calcitriol/physiology[MESH]|Receptors, Retinoic Acid/physiology[MESH]|Retinoid X Receptors[MESH]|Transcription Factors/physiology[MESH]|Vitamin D/metabolism/*physiology[MESH] |
