Metabolism of dihydrotachysterol and 5,6-trans-cholecalciferol in the chick and the rat.
Dihydrotachysterol and 5,6-trans-cholecalciferol are biologically active analogues of cholecalciferol (vitamin D) with a similarity in steric structure to 1,25-dihydroxycholecalciferol, the active form of the vitamin. The question arises as to the nature of the active form of these analogues. High specific radioactivity (14)C- and (3)H-labelled forms of dihydrotachysterol and 5,6-trans-cholecalciferol and its 25-hydroxy derivative were synthesized and their metabolism was studied in chicks and rats. All these steroids were very rapidly metabolized compared with cholecalciferol; 20% of the dihydrotachysterol dose was excreted in bile in the first 24h, about 50% as a carboxylic acid derivative. Although polar metabolites were detected in tissues, no 1-hydroxy form was observed. Larger proportions of the parent steroid and its 25-hydroxy metabolite were detected in tissues compared with cholecalciferol, but no single metabolite was detected at the intracellular site of action of cholecalciferol. It is suggested that analogues of cholecalciferol will be biologically active if they possess a hydroxyl group in the same steric position as that at C-1 of cholecalciferol, with the greatest activity shown by those that also have a C-25 hydroxyl group. The implication of these findings for the chemical features necessary for binding to receptor proteins are briefly discussed.
D000818:Animals; D001646:Bile / Q000032:analysis; D001842:Bone and Bones / Q000032:analysis; D002250:Carbon Radioisotopes; D002645:Chickens; D002762:Cholecalciferol / Q000378:metabolism*; D002845:Chromatography; D002849:Chromatography, Gas; D002850:Chromatography, Gel; D002855:Chromatography, Thin Layer; D004097:Dihydrotachysterol / Q000097:blood / Q000378:metabolism*; D004100:Dihydroxycholecalciferols; D007413:Intestinal Mucosa / Q000032:analysis; D007668:Kidney / Q000032:analysis; D008099:Liver / Q000032:analysis; D009132:Muscles / Q000032:analysis; D051381:Rats; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D014316:Tritium
D002250:Carbon Radioisotopes; D004100:Dihydroxycholecalciferols; D014316:Tritium; D002762:Cholecalciferol; D004097:Dihydrotachysterol