Central Nervous System Control of Hyperphagia in Hypothalamic Obesity: Dependence on Adrenal Glucocorticoids*

Abstract

Gold thioglucose (GTG)-treated hyperphagic obese mice exhibit a pronounced anorexia upon adrenalectomy which is reversed by the systemic administration of adrenal glucocorticoids. To determine whether the return of hyperphagia was mediated by an action of the hormones on the central nervous system, food intake and body weight were monitored in anorexic GTG-treated obese adrenalectomized mice which received a single intracerebroventricular (icv) injection of very small amounts of adrenal glucocorticoids, including cortisone, corticosterone, and dexamethasone. The responses of untreated controls and adrenalectomized control mice were also studied. To rule out possible systemic effects of icv injections of adrenal glucocorticoids, food intake and body weight were also monitored in similar mice given a single ip injection of the hormones. We found that hyperphagia was restored and weight loss abolished in anorexic GTG-treated obses adrenalectomized mice after a single icv injection of adrenal glucocorticoids; the dose of cortisone required was found to be 1/60th of that previously shown to be needed systemically to restore hyperphagia. A single ip injection of these adrenal hormones in the small amounts given icv failed to induced hyperphagia in these mice. The icv and ip injections of the adrenal glucocorticoids did not significantly affect food intake or body weight of untreated controls and adrenalectomized control mice. These findings indicate that adrenal glucocorticoids act via the central nervous system in restoring hyperphagia in anorexic GTG-treated obese adrenalectomized mice.