Add time:08/15/2019         Source:sciencedirect.com

Three A-ring analogs of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3)—2-nor-1,3-seco-1,25(OH)2D3 (2-nor analog), 2-oxa-3-deoxy-25-OH-D3 (2-oxa analog), and A-homo-3-deoxy-3,3-dimethyl-2,4-dioxa-25-OH-D3 (A-homo analog)—were tested for their ability to inhibit 25-OH-D3-1α-hydroxylase (1α-hydroxylase) in isolated mitochondria and to alter 25-OH-D3 metabolism in cultured chick kidney cells. The 2-nor and 2-oxa analogs were relatively potent (Kis of 60 and 30 nM, respectively, compared with 170 nM for 1,25(OH)2D3), whereas the A-homo analog was completely ineffective in inhibiting 1α-hydroxylase activity. In contrast, all three analogs were able to repress 1α-hydroxylase and induce 24-hydroxylase activity in cultured chick kidney cells, suggesting that this process is not one of direct action in the mitochondria, but is more likely to be a receptor-mediated one.

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