Dehydroepiandrosterone (DHEA), a steroid hormone that is secreted by the adrenal cortex in mammals, has an array of biological actions, including inhibition of fat synthesis, decreasing the number of adipocytes, and a reduction in mammalian metabolic efficiency. Recent studies showed that DHEA may decrease fat deposition in poultry, but the mechanism of action is unclear. In the present study, we demonstrate that DHEA stimulates intracellular cyclic adenosine 3 0 ,5 0 -monophosphate (cAMP) accumulation in chicken hepatocytes during a 30 min incubation period. Increases in intracellular cAMP are evoked by as low as 0·1 mM-DHEA. The cAMP induced by DHEA, while suppressing cAMP-specific phosphodiesterase activity, also activates cAMP-dependent protein kinase A (PKA) in chicken hepatocytes. In addition, the activation of PKA leads to down-regulation of sterol regulatory element-binding protein-1 (SREBP-1). These findings demonstrate that direct action by DHEA leads to activation of the cAMP/PKA signalling system in the modulation of lipid metabolism by repressing SREBP-1, thereby providing a novel explanation for some of the underlying effects proposed for DHEA in the prevention of fat deposition in poultry.Dehydroepiandrosterone: Hepatic lipid metabolism: Lipogenesis: Cultured primary chicken hepatocytes Cyclic adenosine 3 0 ,5 0 -monophosphate (cAMP) is an integral constituent of the kinase cascade that links a number of extracellular signals to a variety of cellular functions. Under physiological conditions, the biosynthesis of lipids in the liver is negatively regulated, at least in part, by the elevated intracellular level of cAMP (1 -3) . Glucagon, the adrenalines, and other reagents raise the cellular cAMP concentration level and reduce the activity or level of hepatic lipogenic enzymes (4,5) such as fatty acid synthase, stearoyl-CoA desaturase, and glycerol-3-phosphate acyltransferase. The cAMPdependent kinase, protein kinase A (PKA), which is a major protein kinase activated by cAMP, has been shown to be involved in lipid metabolism as well (6,7) . Hepatic fatty acid synthesis and fatty acid synthesis in cultured hepatocytes, mediated by sterol regulatory element-binding protein (SREBP)-1, a transcription factor that regulates genes controlling intracellular lipid metabolism, have been shown to be negatively affected by cAMP (8) . It has also been demonstrated that cAMP inhibits insulin-regulated SREBP-1 mRNA levels and the expression of the SREBP-1-regulated genes involved in lipogenesis (9) . However, the molecular mechanism underlying this inhibitory function is still unclear.Dehydroepiandrosterone (DHEA), the most abundant steroid hormone in circulation (10)