title: Sexually dimorphic functional alterations of rat hepatic glucocorticoid receptor in response to fluoxetine.
abstract: 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 receptor's 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 (5mg/kg body mass, 21day, 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 both 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.
authors.affiliation: University of Belgrade Institute for Biological Research "Sinisa Stanković", Department of Biochemistry, Serbia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Elaković
authors.forename: Dorde
authors.initials: D
authors.lastname: Vasiljević
authors.forename: Miroslav
authors.initials: M
authors.lastname: Adzic
authors.forename: Ana
authors.initials: A
authors.lastname: Djordjevic
authors.forename: Jelena
authors.initials: J
authors.lastname: Djordjevic
authors.forename: Marija
authors.initials: M
authors.lastname: Radojcić
authors.forename: Gordana
authors.initials: G
authors.lastname: Matić
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000378:metabolism*; D002482:Cellulose / Q000031:analogs & derivatives / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D005260:Female; D005473:Fluoxetine / Q000378:metabolism*; D005938:Glucocorticoids / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D012727:Sex Characteristics
chemical_list: D000928:Antidepressive Agents; C033190:DNA-cellulose; D005938:Glucocorticoids; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D011965:Receptors, Glucocorticoid; D005473:Fluoxetine; D002482:Cellulose; D004247:DNA