Estradiol acts in the medial preoptic area, arcuate nucleus, and dorsal raphe nucleus to reduce food intake in ovariectomized rats

Abstract

Estradiol (E2) exerts an inhibitory effect on food intake in a variety of species. While compelling evidence indicates that central, rather than peripheral, estrogen receptors (ERs) mediate this effect, the exact brain regions involved have yet to be conclusively identified. In order to identify brain regions that are sufficient for E2's anorectic effect, food intake was monitored for 48 h following acute, unilateral, microinfusions of vehicle and two doses (0.25 and 2.5 μg) of a water-soluble form of E2 in multiple brain regions within the hypothalamus and midbrain of ovariectomized rats. Dose-related decreases in 24-h food intake were observed following E2 administration in the medial preoptic area (MPOA), arcuate nucleus (ARC), and dorsal raphe nucleus (DRN). Within the former two brain areas, the larger dose of E2 also decreased 4-h food intake. Food intake was not influenced, however, by similar E2 administration in the paraventricular nucleus, lateral hypothalamus, or ventromedial nucleus. These data suggest that E2-responsive neurons within the MPOA, ARC, and DRN participate in the estrogenic control of food intake and provide specific brain areas for future investigations of the cellular mechanism underlying estradiol's anorexigenic effect.

Fig. 1

Summary of cannula placements. The line drawings represent the cannula placements of rats included in the study. Rats with misplaced cannulae were excluded from data analysis. This resulted in 39 rats being included in the data analysis (MPOA, −0.4 bregma, n=7; ARC, −3.4 bregma, n=6; DRN, −7.8 bregma, n=6; PVN, −1.8 bregma, n=7; LH, −2.6 bregma, n=6; VMH, −2.5 bregma, n=7)

Fig. 2

Food intake following ventricular (i.c.v.) microinfusions of E2. Microinfusions of E2 into the lateral ventricle decreased food intake in OVX rats. (A) The lower (5 μg) dose of E2 decreased 24-h food intake. (B) The higher (10 μg) dose of E2 decreased both 4- and 24-h food intake. *E2 < vehicle at corresponding time points, P < 0.05.

Fig. 3

Food intake following site-specific microinfusions of E2. Microinfusions of E2 in the MPOA, ARC and DRN, but not in the PVN, LH, or VMH decreased food intake in OVX rats. In the MPOA and ARC (A and B, respectively), the larger dose of E2 decreased 4- and 24-h food intake, whereas the smaller dose of E2 decreased 24-h food intake only. In the DRN (C), dose-related decreases in 24-h food intake were observed following E2 treatment. Neither dose of estradiol affected food intake in the PVN (D), LH (E) or VMH (F). *E2 < vehicle at corresponding time points, P < 0.05. **2.5 μg dose of E2 < 0.25 μg dose of E2, P < 0.05.