Activation of Central, But Not Peripheral, Estrogen Receptors Is Necessary for Estradiol’s Anorexigenic Effect in Ovariectomized Rats

Abstract

Estradiol appears to exert its anorexigenic effect by activating nuclear estrogen receptors (ERs), which are expressed widely in peripheral tissues and in the brain. Here, we used ICI-182,780 (ICI), a pure antiestrogen with limited ability to cross the blood-brain barrier, to assess the relative involvement of peripheral vs. central ERs to estradiol's anorexigenic effect. Food intake was measured after peripheral (sc) administration of ICI or vehicle in ovariectomized rats treated with acute injections of estradiol benzoate and sesame oil over a 2-wk period. Uterine weight was assessed as a biological assay of peripheral ER activation. In a second experiment, food intake was measured after central (lateral ventricular) administration of ICI or vehicle in ovariectomized rats receiving acute injections of estradiol benzoate and oil over a period of 10 d. In order to assess the possible spread of ICI from the brain to the periphery, vaginal cytology samples were examined as a biological assay of peripheral ER activation. Peripherally administered ICI failed to attenuate estradiol's anorexigenic effect at a dose that was sufficient to block estradiol's uterotrophic effect. This suggests that peripheral activation of ERs is not necessary for estradiol's anorexigenic effect. Although central infusion of 4 nm ICI blocked estradiol's anorexigenic effect, it did not attenuate estradiol's ability to increase the presence of cornified cells in vaginal cytology samples, suggesting that ICI did not leak into the periphery. We conclude that activation of central, but not peripheral, ERs is necessary for estradiol's anorexigenic effect.