[Agonist-induced down-regulation of hepatic glucocorticoid receptor via peroxisome proliferator-activated receptor in SD rats].

Objective It was reported that a negative feedback loop might exist between pemxisome proliferator-activated receptor alpha (PPARa) and glucocorticoid receptor (GR).However,it is unclear whether GR expression is regulated by PPARct activation.To further demonstrate this possibility,we conducted the present study to investigate the regulatory effects of the PPARα agonist fenofibrate on GR expression in Sprague-Dawley rats.Methods GR gene and protein expression levels were determined in liver,visceral and muscle tissues.Adrenal 11 β-hydroxylase (CYP11B1) expression was examined by RT-PCR and circulating corticosterone level was measured by RIA method.Results GR expression was reduced by fenofibrate in a time-and does-dependent manner.The GR mRNA in the three fenofibrate groups of rats were 55%(FE1),54%(FE2) and 68% (FE3) lower than that of the control rats.The GR protein were 28%.77% and 99% lower than the control.The inhibition was observed in liver,but not in fat and muscle.The coaicosterone level in the blood was increased significantly by fenofibrate (the levels of corticorsterone in control.FE1,FE2,FE3,MK886 groups were (393±23)、(495±44)、(516±18)、(622±93)、(382±37) ng/ml respectively.These effects of fenofibrate were abolished by PPARα inhibitor MK886.suggesting that fenoffbrate activated throush PPARα.Conclusion A new molecular mechanism has been found for a negative feedback regulation of GR activity by PPARα in SD rats. Key words: Peroxisome proliferator-activated receptors; Receptor; glucocorticoid; Negative feedback