INVOLVEMENT OF TYPE-I CORTICOSTEROID RECEPTOR IN THE EFFECTS OF OVARIECTOMY ON ENERGY-BALANCE

The effects of the glucocorticoid receptor antagonist, RU-38486 (RU-48 6), and the mineralocorticoid receptor (MR) antagonist, RU-28318, on e nergy 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 analy zed for energy and nitrogen contents. Energy content was determined by adiabatic bomb calorimetry, whereas nitrogen was determined in 250- t o 300-mg samples of dehydrated carcasses, with the use of the Kjeldahl procedure. The energy as protein was subtracted from total carcass en ergy 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 m easured at the beginning of the experiment. A significant interaction effect of surgery and corticosteroid antagonist was observed on body e nergy gain, energetic efficiency, and fat gain. Whereas body energy ga in, energetic efficiency, and fat gain were larger in OVX rats than in sham-operated animals treated with either placebo or RU-486, they wer e comparable in OVX and sham-operated rats treated with RU-28318. Surg ery, but not corticosteroid antagonist, had a significant effect on di gestible energy intake, energy expenditure, and protein gain. All thes e variables were higher in OVX rats than in sham-operated animals. Sur gery also affected corticosterone levels and adrenal weight. Both of t hese variables were lower in OVX rats than in sham-operated animals. B y demonstrating the ability of RU-28318 to attenuate the effects of OV X on energy balance, the present study provides evidence that NIR occu pation by corticosteroids facilitates the OVX-induced changes in energ y balance.