Dehydroepiandrosterone and related steroids alter 3T3-L1 preadipocyte proliferation and differentiation

The purpose of the present study was to determine if the anti-adipogenic ef fects of dehydroepiandrosterone (DHEA) are mediated solely by DHEA or by on e or more of its downstream metabolites. In Experiment I, preconfluent prol iferating cultures of 3T3-L1 preadipocytes were incubated for either 24 or 72 h with 0, 1, 5 or 25 mu M DHEA. DHEA sulfate (DHEAS), testosterone, estr one and 17 beta-estradiol. Pregnenolone, a precursor of DHEA(S), was also t ested at these concentrations. After 24 h of incubation, DHEAS, 17 beta-est radiol and estrone at the 1 mu M level stimulated preadipocyte proliferatio n. In contrast, DHEA and 17 beta-estradiol at the 25 mu M level attenuated proliferation to a greater extent than all other steroids. After 72 h of in cubation, DHEA and 17 beta-estradiol at the 25 mu M level attenuated prolif eration to a greater extent than all other steroids. In Experiment 2, post- confluent cultures of differentiating 3T3-L1 preadipocytes were incubated f or 6 days with 0, 5, 30, or 60 mu M levels of these steroids. Preadipocyte differentiation, as assessed by lipid content and glycerol-3-phosphate dehy drogenase activity, decreased markedly when treated with 30 and 60 mu M DHE A, 17 beta-estradiol, estrone and pregnenolone. In contrast, DHEAS had no i mpact on preadipocyte proliferation or differentiation. These results sugge st that the anti-adipogenic actions of DHEA in adipose tissue may be mediat ed, in part, by one or more of its distal metabolites, including 17 beta-es tradiol. (C) 1999 Elsevier Science Inc. All rights reserved.