Synthesis and biological activity of vitamin D ₃ 3β-sulfate. Role of vitamin D ₃ sulfates in calcium homeostasis

To determine the biological activity of vitamin D sulfates, we synthesized vitamin D ₃ 3β-sulfate and tested its biological activity in vitamin D-deficient hypocalcemic rats. When vitamin D ₃ sulfate was administered as a single oral dose of 208,000 or 416,000 pmol (100 μg or 200 μg), it increased active calcium transport in the duodenum and was also able to mobilize calcium from bone and soft tissue. Dose levels below this failed to elicit a response. Vitamin D ₃ itself was active at doses as low as 260 pmol when administered in this manner. In order to test the biological activity of vitamin D ₃ sulfate in various doses when administered chronically, we tested the biological activity of vitamin D ₃ sulfate after 5 days of oral dosing: vitamin D ₃ sulfate was active at doses of 52,000 pmol/day (25 μg), whereas vitamin D ₃ was active at doses of 65 to 260 pmol/day over a period of 5 days. When administered as a single intravenous dose, vitamin D ₃ sulfate exhibited no biological activity in doses as high as 52,000 pmol. Vitamin D ₃, however, was active at a dose of as low as 65 pmol. We conclude that vitamin D ₃ sulfate, a metabolite of vitamin D ₃ of heretofore unknown biological activity, is considerably less active than vitamin D ₃ itself.