ru-28318 and Body-Weight

The effects of the glucocorticoid receptor antagonist, RU-38486 (RU-486), and the mineralocorticoid receptor (MR) antagonist, RU-28318, on energy balance were investigated in a 2 [surgery: ovariectomy (OVX) and sham operation] x 3 (corticosteroid antagonist: placebo, RU-28318, RU-486) experimental design. Rats were treated for 28 days. Food intake and body weight were monitored throughout the treatment period. At the end of the treatment, rats were killed and their carcasses were analyzed for energy and nitrogen contents. Energy content was determined by adiabatic bomb calorimetry, whereas nitrogen was determined in 250-to 300-mg samples of dehydrated carcasses, with the use of the Kjeldahl procedure. The energy as protein was subtracted from total carcass energy to determine energy as fat. The gains in energy, fat, and protein were calculated by subtracting the values obtained at the end of the treatment period from initial values estimated from the body weights measured at the beginning of the experiment. A significant interaction effect of surgery and corticosteroid antagonist was observed on body energy gain, energetic efficiency, and fat gain. Whereas body energy gain, energetic efficiency, and fat gain were larger in OVX rats than in sham-operated animals treated with either placebo or RU-486, they were comparable in OVX and sham-operated rats treated with RU-28318. Surgery, but not corticosteroid antagonist, had a significant effect on digestible energy intake, energy expenditure, and protein gain. All these variables were higher in OVX rats than in sham-operated animals. Surgery also affected corticosterone levels and adrenal weight. Both of these variables were lower in OVX rats than in sham-operated animals. By demonstrating the ability of RU-28318 to attenuate the effects of OVX on energy balance, the present study provides evidence that MR occupation by corticosteroids facilitates the OVX-induced changes in energy balance.

Topics: Animals; Body Weight; Energy Metabolism; Female; Lipid Metabolism; Mifepristone; Mineralocorticoid Receptor Antagonists; Ovariectomy; Rats; Rats, Sprague-Dawley; Receptors, Glucocorticoid; Receptors, Mineralocorticoid; Spironolactone

The daily fluid intake of male Wistar rats with simultaneous access to 6% ethanol and water was determined during a baseline period (1 week), following adrenalectomy (1 week) and for 3 weeks following SC implantation of hormone pellets containing corticosterone (CORT) or dexamethasone (DEX). Ethanol consumption dropped during the first week of adrenalectomy (ADX) but increased again in the absence of hormone replacement to reach preoperative levels during the ensuing weeks. The CORT treatment, which produced plasma hormone levels similar to the 24-h mean concentration of adrenally intact rats, not only reversed the effect of ADX on alcohol consumption but also enhanced it to levels above those observed in intact rats. Water intake was not affected by the CORT treatment. DEX implants stimulated water intake, but did not enhance the drinking of ethanol. SC injections of RU 28318 (type I corticosterone receptor antagonist; 10 mg/kg) or mifepristone (RU 38486; type II receptor antagonist; 25 mg/kg) at the beginning and halfway through three daily, 6-h tests failed to affect ethanol drinking in adrenally intact rats or in ADX rats bearing CORT implants. Similarly, there was no effect of giving the two antagonists in combination. These results suggest that exogenous CORT can induce excessive alcohol intake in genetically unselected rats and that this facilitatory effect may be mediated by non-genomic cellular mechanisms.

Topics: Adrenalectomy; Alcohol Drinking; Animals; Body Weight; Corticosterone; Dexamethasone; Drinking; Drug Implants; Male; Mifepristone; Mineralocorticoid Receptor Antagonists; Organ Size; Rats; Rats, Wistar; Receptors, Steroid; Sodium Chloride; Spironolactone