Synthesis of [26,27-3H]-25-hydroxycholecalciferol

Suda, Toshio; DeLuca, Hector; Hallick, Richard B.

doi:10.1016/0003-2697(71)90118-7

Cited by 85 publications

(17 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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…”

Section: Introductionsupporting

confidence: 68%

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

Frolik¹,

DeLuca²

1973

J. Clin. Invest.

View full text Add to dashboard Cite

A B S T R A C r Daily oral administration of 1,25-dihvdroxycholecalciferol to vitamin D-deficient rats increases the rate of disappearance of [3H]1,25-dihydroxycholecalciferol and increases the rate of appearance of metabolites both less polar and more polar than 1,25-dihydroxycholecalciferol in the intestine, bone, liver, kidney, plasma, and muscle. Since 1,25-dihydroxycholecalciferol is believed to be the metabolically active form of vitamin D in the stimulation of intestinal calcium transport and bone calcium mobilization, these results provide an explanation for the fact that daily oral administration of 1,25-dihydroxycholecalciferol is relatively ineffective in the maintenance of serum calcium and in the calcification of bone in rats.

show abstract

Section: Introductionsupporting

confidence: 68%

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

Frolik¹,

DeLuca²

1973

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…The [26,27-3H]25-OHD3 was synthesized in this laboratory (19), while the 1,25-(OH)2D3 was prepared with chicken kidney homogenate (20 (17).…”

Section: Methodsmentioning

confidence: 99%

Control of 25-Hydroxycholecalciferol Metabolism by Parathyroid Glands

Garabédian

Holick

DeLuca

et al. 1972

Proc. Natl. Acad. Sci. U.S.A.

615

198

View full text Add to dashboard Cite

Thyroparathyroidectomy of rats on a diet low in calcium reduces production of 1,25-dihydroxycholecalciferol from 25-hydroxycholecalciferol to negligible levels within 40 hr, and increases production of another metabolite, called Va. Parathyroid extract, at a dose of 20 units per day, prevents these changes. When 40 units per day of parathyroid extract is given 48 hr after thyroparathyroidectomy, 1,25-dihydroxycholecalciferol production is restored almost to control levels within 36 hr. The change brought about by parathyroid extract cannot be attributed to resulting changes in serum calcium or phosphorus concentration. It appears that the parathyroid hormone serves as a tropin for production of 1,25-dihydroxycholecalciferol, the hormonal form of vitamin D responsible for calcium mobilization from intestinal contents and bone.Recently, a hormonal system involved in the regulation of calcium concentration in blood plasma was discovered. This system, which derives its active component from vitamin D, is located in kidney tissue. Vitamin D must first be metabolized in the liver to its 25-hydroxy derivative [25-hydroxycholecalciferol (25-OHD3) ] (1-3). This metabolite is further converted in the kidney to either 1,25-dihydroxycholecalciferol [1,2D.] (4-7) or to an unidentified metabolite designated as Va (8-10). The Va metabolite has not been assigned a function, but evidence is convincing that 1,25-(OH)2D3 is the metabolically active form of vitamin D that induces intestinal calcium absorption (11)(12)(13) and mobilization of calcium from bone (14-16). The synthesis of 1,25-(OH)2D3 is regulated by negative feedback, thus establishing 1,25-(OH)2D3 as a true hormone involved in the regulation of the plasma calcium concentration (17,18). The nature of the feedback regulation, i.e., the sharp shut-off of 1,25-(OH)2D3 synthesis at serum calcium concentrations very close to normal, suggested that the regulation involves secretion of parathyroid hormone. We considered it possible that the parathyroid glands might actually detect low serum calcium concentrations, and that the hormone might actually regulate the synthesis of 1,25-(OH)2D3 in kidney. It is the purpose of this communication to demonstrate that parathyroid hormone is a major factor in the regulation cf 25-OHD3 metabolism that was previously attributed to serum calcium concentration. MATERIALS AND METHODSHormones. Parathyroid extract was a gift from the Eli Lilly Co., Indianapolis, Ind., while highly purified parathyroid hormone was purchased from Wilson Laboratories, Chicago, Ill. The hormone was dissolved in 1 mM acetic acid, to which was added gelatin (15%) and phenol (0.4%). The final concentration was 5 units of hormone per 0.05 ml.The [26,27-3H] Tap water was added to the remaining serum to bring the volume to 5 ml, then 15 ml of methanol-chloroform 2:1 was added. The mixture was allowed to stand overnight at 4°. 5 ml of chloroform was added, the mixture was shaken, and the two phases were allowed to separate. The chloroform phase was drawn off and ...

show abstract

“…However, in contrast to the intestine. the bone calcium mobilization response to both 1,25-(OH) 2D3 and to 25-OHD3 is actinomvcin D sensitive (13 Ci/mmole) (17) using the in vitro chick kidney incubation system previously described by Gray, Boyle, and DeLuca (4) as modified by Boyle, Miravet, Gray, Holick, and DeLuca (12 27-3H]-1,25-(OH)2D3 dissolved in 0.05 ml of 95% ethanol. After the required time interval, the animals were sacrificed.…”

Section: Introductionmentioning

confidence: 99%

Metabolism of 1,25-dihydroxycholecalciferol in the rat

Frolik¹,

DeLuca²

1972

J. Clin. Invest.

View full text Add to dashboard Cite

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.

show abstract

Synthesis of [26,27-3H]-25-hydroxycholecalciferol

Cited by 85 publications

References 13 publications

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

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

Control of 25-Hydroxycholecalciferol Metabolism by Parathyroid Glands

Metabolism of 1,25-dihydroxycholecalciferol in the rat

Contact Info

Product

Resources

About