Nonclassic actions of vitamin D.
BACKGROUND
Vitamin D receptors are found in most tissues, not just those participating in the classic actions of vitamin D such as bone, gut, and kidney. These nonclassic tissues are therefore potential targets for the active metabolite of vitamin D, 1,25(OH)(2)D. Furthermore, many of these tissues also contain the enzyme CYP27B1 capable of producing 1,25(OH)(2)D from the circulating form of vitamin D. This review was intended to highlight the actions of 1,25(OH)(2)D in several of these tissues but starts with a review of vitamin D production, metabolism, and molecular mechanism.


METHODS
Medline was searched for articles describing actions of 1,25(OH)(2)D on parathyroid hormone and insulin secretion, immune responses, keratinocytes, and cancer.


RESULTS
Vitamin D production in the skin provides an efficient source of vitamin D. Subsequent metabolism to 1,25(OH)(2)D within nonrenal tissues differs from that in the kidney. Although vitamin D receptor mediates the actions of 1,25(OH)(2)D, regulation of transcriptional activity is cell specific. 1,25(OH)(2)D inhibits PTH secretion but promotes insulin secretion, inhibits adaptive immunity but promotes innate immunity, and inhibits cell proliferation but stimulates their differentiation.


CONCLUSIONS
The nonclassic actions of vitamin D are cell specific and provide a number of potential new clinical applications for 1,25(OH)(2)D(3) and its analogs. However, the use of vitamin D metabolites and analogs for these applications remains limited by the classic actions of vitamin D leading to hypercalcemia and hypercalcuria.
Veterans Affairs Medical Center (111N), 4150 Clement Street, San Francisco, California 94121, USA. daniel.bikle@ucsf.edu
Daniel
D
Bikle
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002117:Calcitriol / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D010281:Parathyroid Hormone / Q000378:metabolism; D014807:Vitamin D / Q000378:metabolism / Q000494:pharmacology*
D000970:Antineoplastic Agents; D007328:Insulin; D010281:Parathyroid Hormone; D014807:Vitamin D; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D002117:Calcitriol