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.