Tang J J, Krul E S, Schonfeld G
Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110.
Biochem Biophys Res Commun. 1991 Dec 31;181(3):1407-11. doi: 10.1016/0006-291x(91)92095-2.
Testosterone and estrogen alter the hepatic synthesis of apoA-I in castrated inbred strains of mice, but apoA-I mRNA levels remain unaltered, suggesting post-transcriptional regulation of apoA-I production in liver. To test this hypothesis, females of the C3H/HeJ and C57BL/6J strains of mice were castrated and after 2 weeks were given testosterone propionate (Testo 1 microgram/g body weight/day,), 17 beta-estradiol (0.16 or 5 microgram/g/day, E2L, E2H, respectively) or vehicle (placebo) for 14 days (n = 5/group). Liver polysomes were isolated from pooled livers of each group and "run-off" assays were performed. Testo increased apoA-I gene translation to 124% and 171% of controls in C3H and C57BL strains, increased polysomal mRNA levels to 276% and 438% and increased apoA-I synthesis to 181% and 269% of respective controls. Decreases in polysomal "run-off", mRNA levels and apoA-I synthesis were produced by E2H. E2L produced non-parallel changes, i.e., it raised apoA-I synthesis and polysomal apoA-I mRNA, but did not affect rates of translation. The data suggest that sex hormones exert their effects on apoA-I gene expression at the translational level.
睾酮和雌激素可改变去势近交系小鼠肝脏中载脂蛋白A-I（apoA-I）的合成，但apoA-I mRNA水平保持不变，这表明肝脏中apoA-I的产生存在转录后调控。为验证这一假设，将C3H/HeJ和C57BL/6J品系的雌性小鼠去势，2周后分别给予丙酸睾酮（Testo，1微克/克体重/天）、17β-雌二醇（分别为0.16或5微克/克/天，E2L、E2H）或赋形剂（安慰剂），持续14天（每组n = 5）。从每组的合并肝脏中分离出肝脏多核糖体，并进行“连续转录”测定。Testo使C3H和C57品系中apoA-I基因的翻译分别增加至对照的124%和171%，使多核糖体mRNA水平分别增加至276%和438%，并使apoA-I合成分别增加至各自对照的181%和269%。E2H导致多核糖体“连续转录”、mRNA水平和apoA-I合成减少。E2L产生了不平行的变化，即它提高了apoA-I合成和多核糖体apoA-I mRNA，但不影响翻译速率。数据表明，性激素在翻译水平上对apoA-I基因表达发挥作用。
