Abstract
The steroid hormone 1α,25-dihydroxyvitamin D 3 [1α,25(OH) 2D 3] stimulates biological responses via both genomic mechanisms and nongenomic mechanisms (opening of voltage-gated Ca 2+ channels). We report here that the two closed B-ring steroid analogs of 1α,25(OH) 2D 3, 1α,25(OH) 2-7-dehydrocholesterol and 1α,25(OH) 2-lumisterol 3, are able to generate the nongenomic response, transcaltachia, without the ability to compete with the natural metabolite for binding to its nuclear receptor. We propose that the nongenomic membrane associated receptor can accept the ligand in its closed "6-s- cis" conformation whereas the nuclear receptor prefers the extended "6-s- trans" conformer.
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