Vitamin D seco-steroids: Unique molecules with both hormone and possible membranophilic properties
1979; Elsevier BV; Volume: 24; Issue: 9 Linguagem: Inglês
10.1016/0024-3205(79)90359-x
ISSN1879-0631
AutoresAnthony W. Norman, F. Patrick Ross,
Tópico(s)Hormonal Regulation and Hypertension
ResumoThe mode of action of vitamin D3 (a seco steroid with a broken B ring) for calcium and phosphorus homeostasis is mediated at least in part through its metabolic transformation to 1, 25-dihydroxyvitamin D and 24, 25-dihydroxyvitamin D3. A vitamin D endocrine system produces in a carefully regulated fashion amounts of 1, 25(OH)2D3dictated by the calcium needs of the organism. 1, 25(OH)2D3 is known to induce the biosynthesis of a a calcium binding protein in the intestine and kidney via a mechanism similar to that of classic steroid hormones. Evidence for biological effects specifically generated by 24, 25(OH)2D3 D have also been obtained. Definite evidence for the further metabolism of these dihydroxylated metabolites exists; it probably occurs via side chain cleavage with the generation of several new molecules of unknown function. Evaluation of the unique structural aspects of these putative vitamin D metabolites suggests a second set of chemical and biological properties which could link these compounds structurally to the membrane-active polyene antibiotic filipin. These properties may rationalize some reported "rapid biological effects" pertaining to vitamin D and metabolites which hitherto have been difficult to explain in terms of classical steroid hormone theory. A key unresolved question relates to identification of the evolutionary pathways which resulted in the selection of vitamin D seco-steroids rather than classical (with intact rings) steroids for Ca and P homeostasis.
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