ISSN:
1573-904X
Keywords:
estradiol
;
estradiol delivery system
;
food intake
;
body weight
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract 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. Finally, when intact female rats were administered the E2-CDS on the day of diestrus I, rats exhibited cornified vaginal epithelial lavages for 3.5 days, during which weight loss was observed, followed by a 7.8-day period of pseudopregnancy during which animals rapidly gained weight. Collectively, these data indicate that delivery of E2 to the brain with E2-CDS causes a marked decline in body weight and food intake in female rats. The phase of increased body weight which follows this drug-induced weight loss appears to be ovarian dependent, since in ovariectomized rats this phase of response to the drug is not observed.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1015953431333
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