ACUTE, CHRONIC, AND INTERACTIVE EFFECTS OF TYPE-I AND TYPE-II CORTICOSTEROID RECEPTOR STIMULATION ON FEEDING AND WEIGHT-GAIN

Type I (aldosterone) and/or type II (dexamethasone or RU28362) corticosterone receptor agonists were continuously infused in adrenalectomized Sprague-Dawley rats for 28 days at doses of 3.4, 17.2, or 86.2 nmol/day. Additional groups received combined agonist infusions, blank infusions, or sham operations. The type I agonist stimulated body weight gain, and the type II agonists were both suppressive, differing mainly in degree. Although there were a few early effects of these hormones (usually a stage of exaggerated activity), once passed, chronic stimulation was marked by steady or slightly increasing steroid influence on body weight. Throughout the chronic phase of this study there was no departure from a simple opponent model of type I and II ligand actions, and their combination approximated an arithmetic summation of the two separate agonists. This was generally true of feeding as well, although steroid effects on intake were always less pronounced. In contrast to chronic administration, acute combinations of these agonists were highly interactive, producing slight losses then large gains for the aldosterone and RU28362 combinations, but a large gain then small loss for the aldosterone and dexamethasone combination. These results imply that RU28362 and dexamethasone differ in more respects than potency. Because normal endogenous type II stimulation is acute and occurs against a background of type I receptor occupation, mixed agonist interactions are probably the rule for everyday physiological activity, not the exception. © 1990.