Metabolism of 1,25-dihydroxycholecalciferol in the rat

Abstract

A B S T R A C T Administration of 60 pnmoles of 1,25-dihv-droxvcholecalciferol to vitamin D-deficient rats on a low calcium diet gives a maximal intestinal calcium transport response in 7 hr and a maximal bone calcium mobilization response in 12 hr. During the 48 hr after injection of radioactive 1,25-dlihvdroxvclholecalciferol, unchanged 1,2 5-dihydroxyclholecalciferol accounts for 71-98% of the radioactivitv found in the intestine with ininor amounts appearing in more polar metabolites. In the bone, for the 1st 12 hr. 1,25-(illwdroxclcholecailciferol is the major form (75-82%) present while at 24 hr. the anmount of 1,25-dihvcdroxvcholecalciferol decreases with a corresponding rise in the amounts of metaholites both less polar and more polar than the 1,25-dihvdroxvcholecalciferol. Since these metabolies are at their hIihest concentration when bone calcium mobilization is decreasing, they are most likely not responsible for the calcium mobilization observed during the 1st 12 hr. The appearance of water-soluble radioactivity in the kidney, plasma.liver, and muscle 24 hr after 1 ,25-dihvdroxv\cholecalciferol injection has been demonstrated. The present results suggest that, although 1 ,25-dihydroxycholecalciferol is converted to further metabolites in the rat, it is probably the form of vitamin D responsible for initiating intestinal calcium transport and bone calcium miiobilizationi.

Vitamin D plasma binding protein. Turnover and fate in the rabbit.

“…The metabolic pathway for vitamin D implicates many tissues in its formation, transformation, and biological action. Vitamin D itself and its potent metabolite, 1,25(OH)2D3, for example, are recognized to have plasma clearance rates and tissue distributions which are distinct from those of 25(OH)D3 (30,(46)(47)(48). It is therefore difficult to present a unified hypothesis whereby DBP, the only specific binding protein for cholecalciferol sterols in mammalian plasma, plays a delivery function for all these sterols.…”

Effects of Dietary Calcium Restriction and Chronic Thyroparathyroidectomy on the Metabolism of [3H]25-Hydroxyvitamin D3 and the Active Transport of Calcium by Rat Intestine

“…Based on recent studies concerned witlh thle biologic activity of 1,25-(OH)2-D3 and the time course of its formation and localization in target organs, it seems likely that this dihydroxylated metabolite is indeed the major endogenously pro-(luce(l tisstue-active fortim of the l)arent vitamin il initact animiials fe(d low calcium or low phosphor-us diets. Furthermore, it is probable that 1,25-(OH)2-D3 produces the vitamin D-dependent enhancement of intestinal calcium absorption under these conditions (19)(20)(21)(22)(23)(24)(25).…”

The Stimulation of 1,25-Dihydroxycholecalciferol Metabolism in Vitamin D-deficient Rats by 1,25-Dihydroxycholecalciferol Treatment

“…Finally, at the time when 1,25-(OH)2D1 is producing its maximal intestinal calcium transport response, it is the only detectable metabolite in the intestine of chicks (21) and the major metabolite in the intestine of rats (22). Similar results have been obtained with the bone calcium mobilization system (22 (25) (247,000 dpm/62.5 pmol) using the kidney homogenate method originally described by Fraser and Kodicek (14) and modified by Boyle and coworkers (16) (170 dpm/60 pmol) every 12 h for 6 days was administered in 0.1 ml of the oil by stomach tube to each of the nine rats in the third group. On the 7th day, three of the rats in this group received orally 0.1 ml of oil as a control while the remaining six rats were given 58 pmol of high specific activity…”

“…The individual tissues from all rats in a group were pooled. These tissues were then counted, extracted with chloroformmethanol, and the lipid extracts chromatographed on Sephadex LH-20 columns (chloroform: Skellysolve B: methanol, 75: 23: 2, vol/vol) as described previously (22). For the control group, the radioactivity present in the tissues was determined by combustion in a Packard Tri-Carb Sample Oxidizer, (model 305, Packard Instrument Co., Inc., Downers Grove, Ill.) before counting the sample.…”

“…All the rats in the three groups were killed 7 h after their last treatment. Their serum calcium and intestinal calcium transport ratios were determined as described previously (22).…”