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

Abstract

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 mM) 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 mM 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 a (PPARa) and carnitine palmitoyl transferase I mRNA was dramatically enhanced subsequent to treatment with 10 or 100 mM DHEA for periods of time from 6 to 48 h, while there was a decrease in the expression of PPARa in the presence of 10 mM DHEA after 1 and 2 h of exposure, and in the presence of 100 mM DHEA after 2 h of exposure. Hepatocytes treated with 10 or 100 mM 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 mM DHEA at 24, 48 and 72 h. In contrast, 1 mM DHEA administration significantly increased cell survival after 72 h; however, 10 mM 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.

Dehydroepiandrosterone inhibits cell proliferation and improves viability by regulating S phase and mitochondrial permeability in primary rat Leydig cells

“…No significant change was detected in mitochondria number and their configuration in primary Leydig cells following DHEA treatment. However, previous studies have demonstrated that DHEA affects mitochondrial number and configuration in chicken hepatocytes ( 20 ) and the liver of male rats ( 39 ). DHEA also increases fatty acid β-oxidation and enhances mitochondrial respiration, which may be the cause of the decrease in mitochondria number in the rat or chicken liver cells ( 20 , 39 ).…”

“…The method used in the present study was modified from the method described by Tang et al ( 20 ). Briefly, primary rat Leydig cells were cultured in 6-well plates (1×10 6 cells/well) and treated with 1 μ M, 50 μ M and 100 μ M DHEA.…”