Dehydroepiandrosterone activates cyclic adenosine 3 ';,5 ';-monophosphate/protein kinase A signalling and suppresses sterol regulatory element-binding protein-1 expression in cultured primary chicken hepatocytes

作者：Tang Xue; Ma Haitian; Shen Zanming; Zou Sixiang^*; Xu Xijie; Lin Chengzhao

来源：British Journal of Nutrition, 2009, 102(5): 680-686.

DOI：10.1017/S0007114509289021

• Dehydroepiandrosterone
• Hepatic lipid metabolism
• Lipogenesis
• Cultured primary chicken hepatocytes

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';,5';-monophosphate (cAMP) accumulation in chicken hepatocytes during a 30 min incubation period. Increases in intracellular cAMP are evoked by as low as 0.1 mu M-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.

• 出版日期2009-9-14
• 单位复旦大学; 江苏省原子医学研究所; 南京农业大学