Vitamin D-dependent calcium transport.
Vitamin D must be metabolized to 25-OH-D3 or calcidiol in the liver and subsequently to 1,25-(OH)2D3 (calcitriol) in the kidney to produce its physiological actions. Calcitriol stimulates calcium and phosphorus transport reactions in the small intestine and together with parathyroid hormone stimulates calcium transport reactions in bone and kidney. In the small intestine calcitriol brings about its response in a complex manner. It provides a very rapid response on existing villus cells, causing a rise in calcium transport within 6 h postadministration. This transport response subsides by 18 h, and a second response makes its appearance at 24-48 h. This second response is likely to be an action on crypt cells which then migrate into the villus region and bring about calcium transport. The molecular mechanism of calcium transport in the villus cells has been examined. Calcitriol localizes specifically in the nucleus within 0.5 h postadministration, and it does not localize in any of the other cell fractions. A receptor has been discovered for calcitriol, and interaction with this receptor is required for calcitriol to bring about its action in stimulating calcium transport. It is therefore believed that calcitriol, together with receptor, binds to specific portions of nuclear DNA to bring about transcription of specific genes that code for calcium and phosphorus transport proteins. Only one protein induced by calcitriol has been described. It is the calcium-binding protein found in the cytoplasm. Exactly how it functions in calcium transport is in debate, although the time sequence of its appearance appears to be consistent with a role in that system. It is likely that other gene products are induced by calcitriol, and they are currently being characterized. In the neonatal rat, active calcium transport does not make its appearance until 14-16 days postpartum. The intestine is not sensitive to vitamin D or calcitriol prior to this time. This lack of sensitivity is because of the lack of a receptor for calcitriol. The receptor to calcitriol can be precociously induced by hydrocortisone injections, or it can be delayed by adrenalectomy. Incubation of intestine from neonatal rat pups at 14 days postpartum with hydrocortisone brings about in vitro appearance of the receptor molecule. These results and results of studies involving genetic vitamin D resistance strongly suggest that calcitriol must function by interaction with the receptor, presumably by a nuclear mechanism, to bring about intestinal calcium transport. The molecular mechanism, however, remains to be described.
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D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D017317:Annexin A6; D001693:Biological Transport, Active / Q000187:drug effects; D001711:Biotransformation; D002117:Calcitriol / Q000096:biosynthesis / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002136:Calcium, Dietary / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002642:Chick Embryo; D002648:Child; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007015:Hypophosphatemia, Familial / Q000378:metabolism; D007408:Intestinal Absorption / Q000187:drug effects; D007668:Kidney / Q000378:metabolism; D007774:Lactation; D010710:Phosphates / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000378:metabolism; D014158:Transcription, Genetic; D014807:Vitamin D / Q000378:metabolism / Q000502:physiology*
D017317:Annexin A6; D002136:Calcium, Dietary; D002135:Calcium-Binding Proteins; D010710:Phosphates; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; D014807:Vitamin D; D002117:Calcitriol; D002118:Calcium