Hypothalamic implants of dilute estradiol fail to reduce feeding in ovariectomized rats

To investigate further the site where estradiol (E-2) inhibits food intake, we tested the effects on feeding of subcutaneous and intrahypothalamic implants of 10% E-2 benzoate in cholesterol (CHOL) or CHOL alone. E-2 was implanted subcutaneously in Silastic tubes, and intrahypothalamically via bilateral 29-gauge cannulas into the paraventricular nucleus (PVN) or the medial preoptic area (MPA) of ovariectomized (OVX) Sprague-Dawley and Long-Evans rats. Three-day implant periods followed 3-day baseline periods. Rats were allowed ad libitum access to chow and tap water, and food intake and body weight were measured each day. Subcutaneous 10% E-2 implants in Sprague-Dawley rats reduced food intake 21% on Day 2 and 34% on Day 3 (P's<.01) and decreased 3-day body weight gain 11 g (P<.05). In contrast, 10% E-2 implants in the PVN of Sprague-Dawley rats did not change food intake or body weight. Implants of 10% or 20% E-2 in the MPA also failed to decrease food intake. MPA implants of 10% E-2 decreased body weight gain 8 g (P<.05), but MPA implants of 20% E-2 decreased weight gain only 4 g (P>.05). To determine whether the strain of rat affected our negative results on food intake, we implanted 10% E-2 into the PVN of Long-Evans rats. Again, PVN E2 did not decrease food intake significantly in comparison to the pretest baseline. PVN E-2 did, however, decrease body weight gain 5 g and decreased food intake 6% compared to rats with implants of CHOL (both P<.05), but these effects appeared to be due to an increase in feeding in the CHOL group in comparison to their baseline. Finally, CHOL and E-2 implants did not impair the responsivity of the PVN because acute implants of norepinephrine (NE) into the PVN of E-2- or CHOL-treated Long-Evans rats significantly increased food intake. Our results do not support the hypothesis that E-2's actions in either the PVN or the MPA are sufficient to account for its inhibitory effects on feeding. (C) 2002 Elsevier Science Inc. All rights reserved.