Long-term imipramine treatment affects rat brain and pituitary corticosteroid receptors and heat shock proteins levels in a gender-specific manner.
Gender-related differences in the effects of imipramine, on the protein levels of glucocorticoid receptor (GR), and heat shock proteins Hsp90 and Hsp70, as well as on dexamethasone binding to corticosteroid receptors (CRs) in the pituitary, hypothalamus, hippocampus and brain cortex of non-depressed rats were studied. Differences between female and male animals in the GR protein level in the tissues of untreated animals were not noticed. However, imipramine led to opposite changes in the cellular level of GR protein in the brain of female and male rats, as well as to gender- and tissue-specific changes in in vitro dexamethasone binding to GR and mineralocorticoid receptor (MR) in the hippocampus and brain cortex. Gender-related differences in the expression of Hsp90 and Hsp70 were noticed mainly in the hippocampus, only after imipramine treatment. The observed changes in the response of GR to imipramine suggest that this antidepressant may affect both the level of the receptor protein and the mechanisms regulating its binding ability in a gender-related manner.
Elaković
I
I
Department of Biochemistry, Institute for Biological Research Sinisa Stanković, Belgrade, Serbia.
Brkljacić
J
J
Matić
G
G
D000305:Adrenal Cortex Hormones / Q000378:metabolism; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003907:Dexamethasone / Q000378:metabolism; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000187:drug effects / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000187:drug effects / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000187:drug effects* / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism; D007099:Imipramine / Q000494:pharmacology*; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018161:Receptors, Mineralocorticoid / Q000187:drug effects / Q000378:metabolism; D011987:Receptors, Steroid / Q000187:drug effects* / Q000378:metabolism; D012727:Sex Characteristics; D013315:Stress, Psychological / Q000378:metabolism / Q000503:physiopathology
D000305:Adrenal Cortex Hormones; D000929:Antidepressive Agents, Tricyclic; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid; D003907:Dexamethasone; D007099:Imipramine