1alpha-Hydroxy [6-3H]vitamin D3 has been synthesized with a specific activity of 4 Ci/mmol, and its metabolism in rats has been studied. It is rapidly converted to 1alpha,25-dihydroxy [6-3H]vitamin D3 in vivo. Following an intravenous or oral dose, a maximal concentration of 1alpha,25-dihydroxy [6-3H]vitamin D3 is found 2 and 4 hours, respectively, before the maximal intestinal calcium transport response is observed. Similarly, 1alpha,25-dihydroxy[6-3H]vitamin D3 accumulation in bone precedes the bone calcium mobilization response. It appears, therefore, that the biological activity of 1alpha-hydroxyvitamin D3 is largely, if not exclusively, due to its conversion to 1alpha,25-dihydroxy[6-3H]vitamin D3 1alpha-Hydroxy[6-3H]vitamin D3 and 1alpha,25-dihydroxy[6-3H]vitamin D3 appear in intestine equally well after an oral or an intravenous dose of 1alpha-hydroxy[6-3H]vitamin D3. However, much less of both 1alpha-hydroxy[6-3H]vitamin D3 and 1alpha,25-dihydroxy[6-3H]vitamin D3 appears in bone and blood after an oral than after an intravenous dose. A much reduced bone calcium mobilization response is also noted following an oral dose as compared to an intravenous dose of 1alpha-hydroxyvitamin D3, suggesting that oral 1alpha-hydroxyvitamin D3 is not utilized as well as intravenously administered material.

[6- 3 H]-1α-Hydroxyvitamin D 3 was chemically synthesized and its full biological activity and radiochemical purity were demonstrated. With the use of this preparation it has been possible to demonstrate in vivo that in rats the [6- 3 H]-1α-hydroxyvitamin D 3 is converted to [6- 3 H]-1α,25-dihydroxyvitamin D 3 , the natural hormone. In fact, in the intestine and bone of rats given 32 picomoles of [6- 3 H]-1α-hydroxyvitamin D 3 each day for 6 days, more than 80 percent of the lipid-soluble radioactivity exists as [6- 3 H]-1α,25-dihydroxyvitamin D 3 , a finding that suggests that much of the biological effectiveness of 1α-hydroxyvitamin D 3 is due to its conversion to 1α,25-dihydroxyvitamin D 3 .

High activity [6-3H]-1α-hydroxyvitamin D3 has been chemically synthesized and shown to be converted rapidly to 1,25-dihydroxyvitamin D3 in both rats and chicks. This rapid conversion takes place prior to initiation of intestinal calcium transport which suggests that 1α-hydroxyvitamin D3 must be converted to 1,25-dihydroxy-vitamin D3 before it functions, although direct action of 1α-hydroxyvitamin D3 cannot be totally excluded. The conversion of 1α-hydroxyvitamin D3 takes place in the liver and not intestine of the rat. On the other hand, both liver and intestine of chicks can carry out this conversion. The 1α-hydroxyvitamin D3 rapidly disappears from blood and intestine of rats being essentially absent 12 hours after a 325 pmole dose, while the formed 1,25-dihydroxyvitamin D3 persists much longer.

[6-3H]-1alpha-Hydroxyvitamin D3 was chemically synthesized and its full biological activity and radiochemical purity were demonstrated. With the use of this preparation it has been possible to demonstrate in vivo that in rats the [6-3H]-1Alpha-hydroxyvitamin D3 is converted to [6-3H]-1alpha,25-dihydroxyvitamin D3, the natural hormone. In fact, in the intestine and bone of rats given 32 picomoles of [6-3H]-1alpha-hydroxyvitamin D3 each day for 6 days, more than 80 percent of the lipid-soluble radioactivity exists as [6-3H]-1alpha,25-dihydroxyvitamin D3, a finding that suggests that much of the biological effectiveness of 1alpha-hydroxyvitamin D3 is due to its conversion to 1alpha,25-dihydroxyvitamin D3.

(6-/sup 3/H)-1..cap alpha..-Hydroxyvitamin D/sub 3/ was chemically synthesized and its full biological activity and radiochemical purity were demonstrated. With the use of this preparation it has been possible to demonstrate in vivo that in rats the (6-/sup 3/H)-1..cap alpha..-hydroxyvitamin D/sub 3/ is converted to (6-/sup 3/H)-1..cap alpha..,25-dihydroxyvitamin D/sub 3/, the natural hormone. In fact, in the intestine and bone of rats given 32 picomoles of (6-/sup 3/H)-1..cap alpha..-hydroxyvitamin D/sub 3/ each day for 6 days, more than 80 percent of the lipid-soluble radioactivity exists as (6-/sup 3/H)-1..cap alpha..,25-dihydroxyvitamin D/sub 3/, a finding that suggests that much of the biological effectiveness of 1..cap alpha..-hydroxyvitamin D/sub 3/ is due to its conversion to 1..cap alpha..,25-dihydroxyvitamin D/sub 3/.

The compound, 1..cap alpha..-Hydroxy (6-/sup 3/H) vitamin D/sub 3/, has been synthesized with a specific activity of 4 Ci/mmol, and its metabolism in rats has been studied. It is rapidly converted to 1..cap alpha..,25-dihydroxy(6-/sup 3/H)vitamin D/sub 3/ in vivo. Following an intravenous or oral dose, a maximal concentration of 1..cap alpha..,25-dihydroxy(6-/sup 3/H)vitamin D/sub 3/ is found 2 and 4 hours, respectively, before the maximal intestinal calcium transport response is observed. Similarly, 1..cap alpha..,25-dihydroxy(6-/sup 3/H)vitamin D/sub 3/ accumulation in bone precedes the bone calcium mobilization response. It appears, therefore, that the biological activity of 1..cap alpha..-hydroxyvitamin D/sub 3/ is largely, if not exclusively, due to its conversion to 1..cap alpha..,25-dihydroxy(6-/sup 3/H)vitamin D/sub 3/. 1..cap alpha..-Hydroxy(6-/sup 3/H)vitamin D/sub 3/ and 1..cap alpha..,25-dihydroxy(6-/sup 3/H)vitamin D/sub 3/ appear in intestine equally well after an oral or an intravenous dose of 1..cap alpha..-hydroxy(6-/sup 3/H)vitamin D/sub 3/. However, much less of both 1..cap alpha..-hydroxy(6-/sup 3/H)vitamin D/sub 3/ and 1..cap alpha..,25-dihydroxy(6-/sup 3/H)vitamin D3 appears in bone and blood after an oral than after an intravenous dose. A much reduced bone calcium mobilization response is also noted following an oral dose as compared to an intravenous dose of 1..cap alpha..-hydroxyvitamin D/sub 3/, suggesting that oral 1..cap alpha..-hydroxyvitamin D/sub more » 3/ is not utilized as well as intravenously administered material. « less