Peroxisome proliferator-activated receptor alpha agonist-induced down-regulation of hepatic glucocorticoid receptor expression in SD rats.
It was reported that glucocorticoid production was inhibited by fenofibrate through suppression of type-1 11beta-hydroxysteroid dehydrogenase gene expression in liver. The inhibition might be a negative-feedback regulation of glucocorticoid receptor (GR) activity by peroxisome proliferator-activated receptor alpha (PPARalpha), which is quickly induced by glucocorticoid in the liver. However, it is not clear if GR expression is changed by fenofibrate-induced PPARalpha activation. In this study, we tested this possibility in the liver of Sprague-Dawley rats. GR expression was reduced by fenofibrate in a time- and does-dependent manner. The inhibition was observed in liver, but not in fat and muscle. The corticosterone level in the blood was increased significantly by fenofibrate. These effects of fenofibrate were abolished by PPARalpha inhibitor MK886, suggesting that fenofibrate activated through PPARalpha. In conclusion, inhibition of GR expression may represent a new molecular mechanism for the negative feedback regulation of GR activity by PPARalpha.
Chen
Xiang
X
Department of Endocrinology, The Third Affiliated Hospital of Sun Yat-Sen University, 600# Tianhe Road, Guangzhou, Guang Dong 510630, China.
Li
Ming
M
Sun
Weiping
W
Bi
Yan
Y
Cai
Mengyin
M
Liang
Hua
H
Yu
Qiuqiong
Q
He
Xiaoying
X
Weng
Jianping
J
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000311:Adrenal Glands / Q000378:metabolism; D000818:Animals; D003345:Corticosterone / Q000097:blood; D015536:Down-Regulation; D011345:Fenofibrate / Q000494:pharmacology*; D005786:Gene Expression Regulation; D007211:Indoles / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D047493:PPAR alpha / Q000819:agonists*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis* / Q000187:drug effects; D013252:Steroid 11-beta-Hydroxylase / Q000096:biosynthesis; D002722:Chlorobenzenes
D003345:Corticosterone; D011345:Fenofibrate; D007211:Indoles; D047493:PPAR alpha; D011965:Receptors, Glucocorticoid; D013252:Steroid 11-beta-Hydroxylase; C060893:MK-886; D002722:Chlorobenzenes