Simpkins J W, Anderson W R, Dawson R, Bodor N
Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville 32610.
Pharm Res. 1989 Jul;6(7):592-600. doi: 10.1023/a:1015953431333.
Studies were undertaken to determine the effects on body weight of a brain-enhanced chemical delivery system for estradiol. This estradiol-chemical delivery system (E2-CDS) has a long half-life in the brain, where it slowly releases estradiol but is quickly cleared from peripheral tissues. We administered, by a single iv injection, E2-CDS (0.2, 1.0, or 5.0 mg/kg), equimolar doses of another 17-hydroxy-substituted estrogen, estradiol valerate (E2-VAL), or the dimethyl sulfoxide (DMSO) vehicle to female rats. Daily food intake and body weight was determined for 24 days thereafter. E2-CDS caused an initial dose-dependent suppression in body weight for up to 8 days and a suppression in food intake for up to 4 days. In response to E2-VAL, the initial declines in body weight and food intake were lower in magnitude, were shorter in duration, and showed no dose dependency. Following this period of weight loss, E2-CDS-treated rats gained weight at a rate greater than that of the DMSO controls, and at the 0.2- and 1.0-mg/kg doses, body weights achieved were greater than control levels. To determine the role of the ovaries on this biphasic response to E2-CDS, long-term ovariectomized rats were treated with E2-CDS (1.0 mg/kg) or the vehicle and parameters of body weight regulation were determined for 25 days. Ovariectomized rats responded to E2-CDS with a prompt and sustained decrease in body weight which did not recover over the 25-day course of the study. The body-weight loss in ovariectomized rats was associated with a marked reduction in food intake for 8 days.(ABSTRACT TRUNCATED AT 250 WORDS)
开展了多项研究以确定脑增强型雌二醇化学递送系统对体重的影响。这种雌二醇化学递送系统（E2-CDS）在大脑中具有较长的半衰期，它在大脑中缓慢释放雌二醇，但能迅速从外周组织清除。我们通过单次静脉注射，给雌性大鼠施用E2-CDS（0.2、1.0或5.0毫克/千克）、等摩尔剂量的另一种17-羟基取代雌激素戊酸雌二醇（E2-VAL）或二甲基亚砜（DMSO）载体。此后24天测定每日食物摄入量和体重。E2-CDS在长达8天的时间内引起初始剂量依赖性体重抑制，并在长达4天的时间内抑制食物摄入量。对于E2-VAL，体重和食物摄入量的初始下降幅度较小、持续时间较短且无剂量依赖性。在这段体重减轻期之后，用E2-CDS处理的大鼠体重增加速度高于DMSO对照组，在0.2毫克/千克和1.0毫克/千克剂量下，达到的体重高于对照水平。为了确定卵巢在对E2-CDS的这种双相反应中的作用，对长期卵巢切除的大鼠用E2-CDS（1.0毫克/千克）或载体进行处理，并在25天内测定体重调节参数。卵巢切除的大鼠对E2-CDS的反应是体重迅速且持续下降，在研究的25天过程中未恢复。卵巢切除大鼠的体重减轻与8天内食物摄入量的显著减少有关。（摘要截断于250字）
