[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 peroxisome proliferator-activated receptor alpha (PPARalpha) and glucocorticoid receptor (GR). However, it is unclear whether GR expression is regulated by PPARalpha activation. To further demonstrate this possibility, we conducted the present study to investigate the regulatory effects of the PPARalpha 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 11beta-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 corticosterone level in the blood was increased significantly by fenofibrate(the levels of corticosterone 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 PPARalpha inhibitor MK886, suggesting that fenofibrate activated through PPARalpha.


CONCLUSIONS
A new molecular mechanism has been found for a negative feedback regulation of GR activity by PPARalpha in SD rats.
Chen
Xiang
X
Department of Endocrinology, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China.
Li
Ming
M
Sun
Wei-ping
WP
Bi
Yan
Y
Cai
Meng-yin
MY
Liang
Hua
H
Yu
Qiu-qiong
QQ
He
Xiao-ying
XY
Weng
Jian-ping
JP
D000818:Animals; D015536:Down-Regulation; D011345:Fenofibrate / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism*; D008297:Male; D047493:PPAR alpha / Q000819:agonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000378:metabolism*
D047493:PPAR alpha; D011965:Receptors, Glucocorticoid; D011345:Fenofibrate