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)