Opposing Actions of Dehydroepiandrosterone and Corticosterone in Rats

Abstract

The purpose of this study was to determine the impact of dehydroepiandrosterone (DHEA) and corticosterone (CORT) treatment, using implants as a route of administration, on specific hormones, metabolites, and enzymes involved in energy metabolism. Sixty male Sprague-Dawley rats, 325 g initial weight, were implanted subcutaneously for 3 weeks with time-release pellets containing either DHEA or CORT at doses of 0, 10, 25, 50, or 100 mg in this 2 × 5 factorial experiment. In general, body weights and food intakes decreased as the level of steroid hormones increased. In contrast to DHEA treatment, rats receiving the 50- and 100-mg doses of CORT had lighter thymus glands and spleens and heavier epididymal and retroperitoneal fat pads than their controls. Rats treated with 100 mg of DHEA had lowered serum levels of triglycerides and lipid hydroperoxides whereas rats treated with 100 mg of CORT had higher levels of these blood lipids compared to their respective controls. In contrast to DHEA treatment, there was a dose-dependent increase in liver lipid content and the specific activities of the hepatic lipogenic enzymes glucose-6-phosphate de-hydrogenase, malic enzyme, and fatty acid synthase in response to CORT treatment. Rats treated with 100 mg of DHEA had higher serum levels of IGF-1 than control rats. Conversely, rats treated with 100 mg of CORT had lower serum levels of IGF-1 and higher serum levels of testosterone, progesterone, and insulin than their controls. These data demonstrate the lipogenic actions of corticosterone in rats. Conversely, DHEA treatment reduced serum and hepatic lipids. Furthermore, these data suggest that using implants instead of bolus injections of steroids may be a more physiological approach for studying the influence of these steroids on lipid metabolism.