Fischer G M, Bashey R I, Rosenbaum H, Lyttle C R
Exp Mol Pathol. 1985 Dec;43(3):288-96. doi: 10.1016/0014-4800(85)90066-8.
Female rabbits on an atherogenic diet were treated with cottonseed oil (control), tamoxifen, testosterone, or progesterone. After 10 weeks the rabbits were killed, the aortas quickly removed, graded for atherosclerosis, and incubated with [14C]proline to determine collagen and elastin synthesis. Rabbits treated with testosterone and progesterone had the greatest degree of atherosclerosis, the highest DPM in hydroxyproline of collagen and elastin, and the greatest accumulation of collagen and elastin in the aorta. Tamoxifen-treated rabbits had less incorporation of radioactivity. In separate experiments aortas of similarly treated rabbits were analyzed for estradiol and progesterone receptor density. These receptors were found to be present, and progesterone and testosterone administration caused a translocation of progesterone receptors from cytosol to nucleus. Results are consistent with the hypothesis that sex hormones can affect the development of atherosclerosis through a direct effect of the hormones on arterial wall to alter collagen and elastin synthesis, the effect being mediated through hormone receptors in the wall.
给食用致动脉粥样化饮食的雌性兔子分别用棉籽油(对照)、他莫昔芬、睾酮或孕酮进行处理。10周后处死兔子,迅速取出主动脉,对动脉粥样硬化进行分级,并用[14C]脯氨酸孵育以测定胶原蛋白和弹性蛋白的合成。用睾酮和孕酮处理的兔子动脉粥样硬化程度最高,胶原蛋白和弹性蛋白羟脯氨酸中的每分钟衰变数(DPM)最高,主动脉中胶原蛋白和弹性蛋白的积累量最大。用他莫昔芬处理的兔子放射性掺入较少。在单独的实验中,对经类似处理的兔子的主动脉进行分析,以测定雌二醇和孕酮受体密度。发现存在这些受体,给予孕酮和睾酮会导致孕酮受体从细胞质转移到细胞核。结果与以下假设一致:性激素可通过激素对动脉壁的直接作用影响动脉粥样硬化的发展,从而改变胶原蛋白和弹性蛋白的合成,这种作用是通过动脉壁中的激素受体介导的。