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

• Published in: Comparative biochemistry and physiology. C, Comparative pharmacology and toxicology Comparative pharmacology and toxicology, 1999-05, Vol.123 (1), p.17-25
• Main Authors: Lea-Currie, Y.Renee, Monroe, Dayle, Mcintosh, Michael K.
• Format: Article
• Language: English
• Subjects: 3T3 Cells - cytology; 3T3 Cells - drug effects; 3T3-L1 preadipocytes; Adipose Tissue - cytology; Animals; Cell Count - drug effects; Cell Differentiation - drug effects; Cell Division - drug effects; Dehydroepiandrosterone - pharmacology; Dehydroepiandrosterone Sulfate - pharmacology; DHEA; Differentiation; Estrogens; Estrogens - pharmacology; L Cells (Cell Line) - cytology; L Cells (Cell Line) - drug effects; Mice; Proliferation; Testosterone - pharmacology
• ISSN: 0742-8413; 1367-8280
• DOI: 10.1016/S0742-8413(99)00003-1

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 μM DHEA, DHEA sulfate (DHEAS), testosterone, estrone and 17β-estradiol. Pregnenolone, a precursor of DHEA(S), was also tested at these concentrations. After 24 h of incubation, DHEAS, 17β-estradiol and estrone at the 1 μM level stimulated preadipocyte proliferation. In contrast, DHEA and 17β-estradiol at the 25 μM level attenuated proliferation to a greater extent than all other steroids. After 72 h of incubation, DHEA and 17β-estradiol at the 25 μM 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 μM 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 μM DHEA, 17β-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 17β-estradiol.