Adrenalectomy and dexamethasone treatment alter the patterns of basal and acute phase response-induced expression of acute phase protein genes in rat liver

• Published in: The Journal of steroid biochemistry and molecular biology 1998-09, Vol.66 (5), p.347-353
• Main Authors: Ševaljević, Ljiljana, Mačvanin, Mirjana, Žakula, Zorica, Kanazir, Dušan T, Ribarac-Stepić, Nevena
• Format: Article
• Language: English
• Subjects: Acute-Phase Proteins - genetics; Acute-Phase Reaction - metabolism; Adrenalectomy; Animals; Biological and medical sciences; Cytokines - physiology; Dexamethasone - pharmacology; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; Glucocorticoids - pharmacology; Glucocorticoids - physiology; Inflammation; Liver - metabolism; Male; Molecular and cellular biology; Rats; Rats, Wistar; RNA, Messenger - analysis; Turpentine - pharmacology; Tyrosine Transaminase - genetics
• ISSN: 0960-0760; 1879-1220
• DOI: 10.1016/S0960-0760(98)00060-0

Hormonal requirements for full hepatic expression of α 2-macroglobulin ( α 2M), α 1-acid glycoprotein (AGP), haptoglobin (Hp) and γ-fibrinogen (Fb) were assessed at the level of mRNA. Prior to exposure to turpentine-induced inflammation, rats were either depleted of glucocorticoids by adrenalectomy or supplemented with an excess of dexamethasone. Adrenalectomy alone did not affect the basal level of acute phase protein (APP) expression except for α 2M mRNA, the level of which was enhanced. In contrast, dexamethasone treatment alone promoted full induction of α 2M, significant, but not maximal increase of AGP and Hp mRNAs and suppression of Fb. In adrenalectomized rats, acute phase (AP)-cytokines, released in response to inflammation, promoted full expression of Fb and Hp and increased the level of AGP mRNA whereas α 2M mRNA remained at the basal level. Inflammation in dexamethasone pretreated rats elicited changes which, in comparison to mRNA values for dexamethasone unpretreated inflamed rats, were seen as overexpression of α 2M, full expression of AGP and incomplete expression of Hp, whereas Fb mRNA remained at the basal level. These data suggest that glucocorticoids are the principal inducers of α 2M and AP-cytokines of Fb. For full induction of AGP, additive actions of glucocorticoids and AP-cytokines are required whereas expression of Hp is predominantly controlled by AP-cytokines.