Down-regulation of glucocorticoid receptor and its relationship to the induction of rat liver tyrosine aminotransferase.
Administration of polyvinyl alcohol containing hydrocortisone (F-PVA) to rats twice caused a rapid increase of plasma glucocorticoids (GCs) around 30 micrograms/dl for 3 days. This rise led to decrease of glucocorticoid receptor (GR) in rat liver cytosol and spleen cells 1 h post F-PVA and remained at low level for more than 10 days. Two hours after administration of hydrocortisone 5 mg/100 g b. wt, the liver tyrosine aminotransferase (TAT) activity in normal rats increased from 13.5 +/- 2.9 to 50.7 +/- 8.9 units, while in rats injected with F-PVA 3 days ago it increased only from 13.9 +/- 2.3 to 21.0 +/- 6.3 U. The inductivity of rat liver remained low at 7, 11 and 20 days after the injection of F-PVA and recovered 30 days later. This study demonstrates the presence of down-regulation of GR in intact animal, and shows that the decrease of GR is accompanied by reduction of target organ response to GCs.
Yang
Y L
YL
Department of Pathophysiology, Second Military Medical College, Shanghai, China.
Tan
J X
JX
Xu
R B
RB
D000315:Adrenalectomy; D000818:Animals; D001921:Brain / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004790:Enzyme Induction; D005260:Female; D005938:Glucocorticoids / Q000097:blood; D006854:Hydrocortisone / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011142:Polyvinyl Alcohol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000378:metabolism*; D012016:Reference Values; D014444:Tyrosine Transaminase / Q000096:biosynthesis*
D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D011142:Polyvinyl Alcohol; D014444:Tyrosine Transaminase; D006854:Hydrocortisone