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Mechanisms for the selective action of Vitamin D analogs
Roger Bouillon1, Lieve Verlinden, Guy Eelen
1Laboratorium voor Experimentele Geneeskunde en Endocrinologie, Katholieke Universiteit Leuven, Onderwijs en Navorsing, 9th floor, Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium. roger.bouillon@med.kuleuven.be
Abstract:
The non-classical effects of 1,25(OH)(2)D(3) create possible therapeutic applications for immune modulation (e.g. auto-immune diseases and graft rejection), inhibition of cell proliferation (e.g. psoriasis, cancer) and induction of cell differentiation (e.g. cancer). The major drawback related to the use of 1,25(OH)(2)D(3) is its calcemic effect, which prevents the application of pharmacological concentrations. Several analogs are now available that show modest to good selectivity with regard to specific effects (e.g. anticancer or immune effects or bone anabolism versus hypercalcemia) when tested in appropriate in vivo models. The molecular basis for this selectivity is only partially understood and probably a variable mixture of mechanisms.
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