An evaluation of the biologic activity and vitamin D receptor binding affinity of the photoisomers of vitamin D3 and previtamin D3.
Level 5 - mechanism / opinion, no new human data
In vitro cell culture and receptor binding study
PubMed 10876100 · doi:10.1016/s0955-2863(00)00077-2
What was done
Researchers evaluated the antiproliferative activity of major photoisomers of vitamin D3, previtamin D3, and their metabolites in cultured human keratinocytes by measuring [3H]-thymidine incorporation into DNA. They also determined the dissociation constants (Kd) of these compounds for the vitamin D receptor (VDR) to assess binding affinity.
What was found
25-Hydroxytachysterol3 was approximately 10- to 100-fold more active than tachysterol3 at inhibiting keratinocyte proliferation. Lumisterol, tachysterol3, 5,6-trans-vitamin D3, and 25-hydroxy-5,6-trans-vitamin D3 produced significant inhibition only at 10^-6 M, while 7-dehydrocholesterol was inactive even at 10^-6 M. Dissociation constants for VDR were 22 nM for 25-hydroxytachysterol3, 58 nM for 25-hydroxy-5,6-trans-vitamin D3, and 560 nM for 5,6-trans-vitamin D3, whereas Kd values for 7-dehydrocholesterol, tachysterol, and lumisterol exceeded 20 µM. Antiproliferative activity did not correlate directly with VDR binding affinity.
Why it matters
The findings demonstrate that cutaneously generated photoisomers of vitamin D and previtamin D possess biological activity in human skin cells that may operate through local metabolic conversion or alternative non-VDR pathways.
Limits
This was an in vitro cell culture and binding assay without in vivo human or animal verification. The abstract omits sample sizes, replicate numbers, variance metrics, and the specific identity of the compound described as active at both 10^-8 and 10^-6 M. Mechanistic pathways and alternative receptors were proposed but not proven.
Cited by
- supports When UVB light strikes cholesterol in the skin, 15 to 20 other photoproduct chemicals are synthesized alongside vitamin D3.