Strain differences in the dose-response curves of adrenalectomized, starved-refed rats to dehydroepiandrosterone (DHEA)

The effects of adrenalectomy and dehydroepiandrosterone (DHEA) doses (0, 15, 30, 60, 120 and 240 mg/kg/day ip) on hepatic enzyme activity and lipid content and on the amount of epididymal fat pad lipid were studied in starved-refed BHE and Sprague-Dawley rats. BHE rats had significantly greater relative liver size, glucose-6-phosphate dehydrogenase (G6PD) and malic enzyme (ME) activities, and percentage liver lipid but less epididymal fat pad lipid than Sprague-Dawley rats. Adrenalectomized (ADX) rats consumed significantly less food, gained less weight per day, and had less lipid in their livers and fat pads than intact rats. As the level of DHEA increased from 0 to 240 mg/kg/day there was a significant linear decrease in average daily weight gain, food intake, G6PD activity, and percentage liver lipid. At the 15 mg/kg/day dose, G6PD activity was significantly reduced without reductions in the other parameters measured. At the 120 mg/kg/day dose, however, weight gain, food intake, G6PD activity, and percentage liver lipid were significantly lower than that of the controls. At this dose DHEA treatment reduced food intake by 17% whereas it diminished average daily weight gain and G6PD activity by 30 and 56%, respectively. The 240 mg/kg/day dose of DHEA significantly reduced food intake, weight gain, liver lipid, G6PD activity, and ME activity. Intact and ADX BHE rats reduced their G6PD activity and liver lipid more rapidly than Sprague-Dawley rats as the level of DHEA administered increased. ADX Sprague-Dawley rats receiving DHEA had greater liver lipid content and enzyme activity than their intact counterparts whereas the reverse situation was true in BHE rats. These data indicate that the effect of DHEA on body weight gain, food intake, and hepatic and peripheral adiposity are dependent on the strain of rat, the adrenal status, and the DHEA dose.