Simpkins J W, Anderson W R, Dawson R, Seth A, Brewster M, Estes K S, Bodor N
Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville 32610.
Physiol Behav. 1988;44(4-5):573-80. doi: 10.1016/0031-9384(88)90321-6.
Studies were undertaken to determine the effects on body weight and food intake of a chemical delivery system which preferentially delivers estradiol (E2) to the brain and there serves as a source for the sustained release of the steroid. We injected intravenously various doses of this estradiol-chemical delivery system (E2-CDS), E2-valerate (E2-VAL) or the dimethyl sulfoxide (DMSO) vehicle to young lean male rats and monitored body weight and 24 hr food intake for 39 days postinjection. E2-VAL caused a transient reduction in food intake and body weight gain. By contrast, a single injection of E2-CDS caused a chronic, dose-dependent reduction in the rate of body weight gain. In these lean rats, the duration of reduced body weight gain was not correlated with the observed transient reduction in food intake. In aged, obese male rats, E2-CDS caused a marked and chronic dose-dependent reduction in body weight. In contrast to lean rats, E2-CDS caused a long-term reduction in food intake in obese rats. To evaluate the importance of the E2-CDS-induced reduction in food intake in the observed persistent weight loss in obese rats, E2-CDS was administered to a group of obese rats and a second group which received the DMSO vehicle was pair-fed an equivalent amount of food daily. The resulting weight loss in both groups was equivalent. These results show that the enhanced delivery of E2 to the brain with the E2-CDS causes sustained reduction in the rate of body weight gain in lean rats and persistent weight loss in obese animals.
开展了多项研究，以确定一种化学递送系统对体重和食物摄入量的影响，该系统优先将雌二醇（E2）递送至大脑，并在大脑中作为类固醇持续释放的来源。我们给年轻的瘦雄性大鼠静脉注射不同剂量的这种雌二醇化学递送系统（E2-CDS）、戊酸雌二醇（E2-VAL）或二甲基亚砜（DMSO）载体，并在注射后39天监测体重和24小时食物摄入量。E2-VAL导致食物摄入量和体重增加出现短暂减少。相比之下，单次注射E2-CDS导致体重增加速率出现慢性、剂量依赖性降低。在这些瘦大鼠中，体重增加减少的持续时间与观察到的食物摄入量短暂减少无关。在老年肥胖雄性大鼠中，E2-CDS导致体重显著且慢性剂量依赖性降低。与瘦大鼠不同，E2-CDS导致肥胖大鼠食物摄入量长期减少。为了评估E2-CDS诱导的食物摄入量减少在肥胖大鼠观察到的持续体重减轻中的重要性，给一组肥胖大鼠施用E2-CDS，并给接受DMSO载体的第二组大鼠每天配对喂食等量的食物。两组产生的体重减轻相当。这些结果表明，通过E2-CDS增强E2向大脑的递送会导致瘦大鼠体重增加速率持续降低，肥胖动物体重持续减轻。
