The effect of dehydroepiandrosterone on lipogenic gene mRNA expression in cultured primary chicken hepatocytes

The effects of dehydroepiandrosterone (DHEA) on lipogenic gene mRNA expression were examined using cultured primary chicken hepatocytes. Cell samples were equilibrated to culture conditions for 24 h and then exposed to DHEA (1, 10 and 100 μM) dissolved in DMSO. The expression of sterol regulatory element-binding protein-1 (SREBP-1) mRNA in cultured primary hepatocytes did not vary with time, except for a significant decrease in gene expression when cells were treated with 10 or 100 μM DHEA for either 1 or 2 h. A similar tendency toward decreased gene expression was evident for acetyl CoA carboxylase. The expression of peroxisome proliferator-activated receptor α (PPARα) and carnitine palmitoyl transferase I mRNA was dramatically enhanced subsequent to treatment with 10 or 100 μM DHEA for periods of time from 6 to 48 h, while there was a decrease in the expression of PPARα in the presence of 10 μM DHEA after 1 and 2 h of exposure, and in the presence of 100 μM DHEA after 2 h of exposure. Hepatocytes treated with 10 or 100 μM DHEA contained more mitochondria and mitochondria with a higher electron density than did untreated hepatocytes. Furthermore, cell survival was significantly inhibited by treatment with 100 μM DHEA at 24, 48 and 72 h. In contrast, 1 μM DHEA administration sig- nificantly increased cell survival after 72 h; however, 10 μM DHEA treatment had no pronounced effect on cell survival. Overall, the results reported here indicate that DHEA accelerates lipid catabolism by direct regulation of hepatic gene expression and by induction of changes in hepatocyte mitochondria.