Sexually dimorphic functional alterations of rat hepatic glucocorticoid receptor in response to fluoxetine
Đorđević, Ana D.
Đorđević, Jelena D.
Radoičić, Marija B.
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Gender-related differences in the expression and functional properties of the hepatic glucocorticoid receptor were studied before and after antidepressant fluoxetine administration to both unstressed and rats exposed to a chronic social isolation stress. Some of the receptors functional properties, including hormone-binding capacity (B-max), hormone-binding potency (B-max/K-D ratio) and the DNA-binding ability, were found to be sexually dimorphic. Fluoxetine treatment (5 mg/kg body mass, 21 day, intraperitoneally) induced a decrease in B-max and in the amount of Hsp70 co-immunoprecipitated with the glucocorticoid receptor only in males, and stimulated the association of the receptor with Hsp90 in females. When applied during the last three weeks of the 6-week isolation, fluoxetine parallelly elevated B-max and the receptor protein level in female animals, while in males diminished B-max and inhibited association of the receptor with Hsp70. Binding of dexamethasone-receptor complexes bo...th to DNA-cellulose and to isolated liver nuclei did not appear to be a target for fluoxetine action. The results point to sex-related differences in the glucocorticoid receptor functioning and in its response to fluoxetine, and suggest that these differences may contribute to well known sexual dimorphism in the sensitivity to stress, to stress-related disorders and to antidepressant treatment. (C) 2010 Elsevier B.V. All rights reserved.
Keywords:Glucocorticoid receptor / Gender differences / Heat shock proteins / Antidepressant fluoxetine / Isolation stress / Rat liver
Source:European Journal of Pharmacology, 2010, 632, 1-3, 79-85
- Ministry of Science of the Republic of Serbia [143003, 143042B]