Qaw F, Schroeder N J, Calverley M J, Trafford D J, Makin H L, Jones G
Department of Biochemistry, Queen's University, Kingston, Ontario, Canada.
J Steroid Biochem Mol Biol. 1992 Mar;41(3-8):859-70. doi: 10.1016/0960-0760(92)90439-p.
The metabolism of dihydrotachysterol (DHT), a hydrogenated analogue of vitamin D, has been studied in vivo using man and rat and in vitro using the perfused rat kidney, and hepatoma (3B) and osteosarcoma (UMR-106) cell lines. In vivo a large number of metabolites appeared in the plasma of rats given DHT2 and DHT3. Of particular interest was a compound more polar than 25-hydroxy-DHT, which has been designated compound H. Further study of this compound showed that it was composed of two components, one (Ha) being in much lower concentration than the other (Hb). The production of T2/H (peak H from DHT2) was demonstrated in human plasma after administration of oral DHT2. Comparison of the metabolites formed in vivo with those isolated from the rat kidney perfused with 25-hydroxy-DHT3 in vitro showed that 25-hydroxy-DHT3 was metabolized along two metabolic pathways previously described for vitamin D, culminating in the production of 25-hydroxy-DHT3-23,26-lactone and 23,25-dihydroxy-24-oxo-DHT3. The osteosarcoma cell line metabolized 25-OH-DHT3 in vitro along the same two metabolic pathways already demonstrated in the perfused rat kidney. More polar metabolites than compound H seen in rat plasma in vivo were shown to be metabolites of compound H and similar metabolites were also produced in the osteosarcoma cell line from chemically synthesized 1 alpha,25-dihydroxy-DHT3. The hepatoma cell line 25-hydroxylated DHT and no feed-back inhibition was observed. Use of the hepatoma cell to 25-hydroxylate a number of chemically synthesized 1-hydroxy-DHTs indicated that compound Ha was indistinguishable from 1 alpha,25-dihydroxy-DHT whereas compound Hb is possibly 1 beta,25-dihydroxy-DHT. Studies with the VDR in both chick gut and calf thymus indicated that 1 alpha,25-dihydroxy-DHT is very effective in displacing radiolabelled 1 alpha,25-dihydroxyvitamin-D3 and is thus most likely to be the calcaemic metabolite of DHT.
已利用人和大鼠在体内、以及利用灌注大鼠肾脏、肝癌（3B）和骨肉瘤（UMR-106）细胞系在体外研究了维生素D的氢化类似物二氢速甾醇（DHT）的代谢情况。在体内，给予DHT2和DHT3的大鼠血浆中出现了大量代谢物。特别令人感兴趣的是一种比25-羟基-DHT极性更强的化合物，它被命名为化合物H。对该化合物的进一步研究表明，它由两种成分组成，一种（Ha）的浓度远低于另一种（Hb）。口服DHT2后，人体血浆中出现了T2/H（来自DHT2的峰H）。将体内形成的代谢物与体外灌注25-羟基-DHT3的大鼠肾脏中分离出的代谢物进行比较，结果表明，25-羟基-DHT3沿着先前描述的维生素D的两条代谢途径进行代谢，最终生成25-羟基-DHT3-23,26-内酯和23,25-二羟基-24-氧代-DHT3。骨肉瘤细胞系在体外沿着与灌注大鼠肾脏中已证实的相同的两条代谢途径代谢25-OH-DHT3。体内在大鼠血浆中所见的比化合物H极性更强的代谢物被证明是化合物H的代谢物，并且在骨肉瘤细胞系中，由化学合成的1α,25-二羟基-DHT3也产生了类似的代谢物。肝癌细胞系对DHT进行25-羟化，未观察到反馈抑制。利用肝癌细胞对多种化学合成的1-羟基-DHT进行25-羟化表明，化合物Ha与1α,25-二羟基-DHT无法区分，而化合物Hb可能是1β,25-二羟基-DHT。在鸡肠道和小牛胸腺中对维生素D受体进行的研究表明，1α,25-二羟基-DHT在置换放射性标记的1α,25-二羟基维生素-D3方面非常有效，因此很可能是DHT的血钙代谢物。
