Imai K, Kudo N, Koyam M, Shirahata A, Kawashim Y
Department of Pharmacy, Saitama Cardiovascular and Respiratory Center, Osato, Saitama, Japan.
Jpn J Pharmacol. 2001 Aug;86(4):437-47. doi: 10.1254/jjp.86.437.
The purpose of the present study is to answer the question of whether there is a species difference in the effects of a pharmacological dose of dehydroepiandrosterone (DHEA) on the enzymes that participate in oleic acid (18:1) formation in the liver. Feeding a diet containing 0.5% (w/w) DHEA for 14 days markedly increased the activities of acyl-coenzyme A (CoA) synthetase, palmitoyl-CoA chain elongase and stearoyl-CoA desaturase in the liver of rats and mice. These enzyme activities, however, were not changed by DHEA in guinea pigs. The treatments of rats and mice with DHEA markedly increased proportions of 18:1 in hepatic lipids, especially phosphatidylcholine (selectively at C-2 position), triacylglycerol and cholesterol ester. DHEA caused no significant changes in acyl compositions of hepatic lipids of guinea pigs. The levels of DHEA or dehydroepiandrosterone sulfate (DHEAS) were markedly increased in serum and livers by DHEA administration to rats, mice and guinea pigs. High correlations were observed between hepatic levels of DHEA or DHEAS and stearoyl-CoA desaturase activities in rats. These results indicate that there are species differences in the inducing effects of DHEA or DHEAS on hepatic formation of 18:1 and that guinea pigs lack the machinery to induce the enzymes.
本研究的目的是回答药理学剂量的脱氢表雄酮（DHEA）对参与肝脏中油酸（18:1）形成的酶的影响是否存在物种差异这一问题。给大鼠和小鼠喂食含0.5%（w/w）DHEA的饲料14天，可显著提高肝脏中酰基辅酶A（CoA）合成酶、棕榈酰CoA链延长酶和硬脂酰CoA去饱和酶的活性。然而，在豚鼠中，这些酶的活性并未因DHEA而改变。用DHEA处理大鼠和小鼠，可显著提高肝脏脂质中18:1的比例，尤其是磷脂酰胆碱（在C-2位选择性增加）、三酰甘油和胆固醇酯。DHEA对豚鼠肝脏脂质的酰基组成没有显著影响。给大鼠、小鼠和豚鼠注射DHEA后，血清和肝脏中DHEA或硫酸脱氢表雄酮（DHEAS）的水平显著升高。在大鼠中，观察到肝脏中DHEA或DHEAS水平与硬脂酰CoA去饱和酶活性之间存在高度相关性。这些结果表明，DHEA或DHEAS对肝脏中18:1形成的诱导作用存在物种差异，且豚鼠缺乏诱导这些酶的机制。
