Dehydroepiandrosterone and related steroids alter 3T3-L1 preadipocyte proliferation and differentiation.
The purpose of the present study was to determine if the anti-adipogenic effects of dehydroepiandrosterone (DHEA) are mediated solely by DHEA or by one or more of its downstream metabolites. In Experiment 1, preconfluent proliferating cultures of 3T3-L1 preadipocytes were incubated for either 24 or 72 h with 0, 1, 5 or 25 microM DHEA, DHEA sulfate (DHEAS), testosterone, estrone and 17beta-estradiol. Pregnenolone, a precursor of DHEA(S), was also tested at these concentrations. After 24 h of incubation, DHEAS, 17beta-estradiol and estrone at the 1 microM level stimulated preadipocyte proliferation. In contrast, DHEA and 17beta-estradiol at the 25 microM level attenuated proliferation to a greater extent than all other steroids. After 72 h of incubation, DHEA and 17beta-estradiol at the 25 microM level attenuated proliferation to a greater extent than all other steroids. In Experiment 2, post-confluent cultures of differentiating 3T3-L1 preadipocytes were incubated for 6 days with 0, 5, 30, or 60 microM levels of these steroids. Preadipocyte differentiation, as assessed by lipid content and glycerol-3-phosphate dehydrogenase activity, decreased markedly when treated with 30 and 60 microM DHEA, 17beta-estradiol, estrone and pregnenolone. In contrast, DHEAS had no impact on preadipocyte proliferation or differentiation. These results suggest that the anti-adipogenic actions of DHEA in adipose tissue may be mediated, in part, by one or more of its distal metabolites, including 17beta-estradiol.
Lea-Currie
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Department of Nutrition, and Food Service Systems, School of Human Environmental Sciences, University of North Carolina at Greensboro, 27402-6170, USA.
Monroe
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Mcintosh
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D016475:3T3 Cells / Q000166:cytology* / Q000187:drug effects; D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D002452:Cell Count / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D019314:Dehydroepiandrosterone Sulfate / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D007739:L Cells / Q000166:cytology / Q000187:drug effects; D051379:Mice; D013739:Testosterone / Q000494:pharmacology*
D004967:Estrogens; D013739:Testosterone; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate