Research ReportGender-specific response of brain corticosteroid receptors to stress and fluoxetine

Gender-related differences in dexamethasone binding to corticosteroid receptors (CR) and in glucocorticoid receptor (GR) protein level in the pituitary, hypothalamus, hippocampus and prefrontal cortex were studied before and after antidepressant fluoxetine administration to both unstressed and rats exposed to a chronic social isolation stress. Untreated males, in comparison to females, displayed higher hormone-binding capacity of both GR and mineralocorticoid receptor (MR) in the hippocampal cytosol, as well as higher GR protein level in the pituitary cytosol. In both genders, dexamethasone binding to MR exceeded that to GR. While fluoxetine treatment and social isolation had no effect on GR activity, the influence on MR was gender-specific. Fluoxetine facilitated MR hormone-binding only in females, increasing the MR/GR activity ratio. In contrast, after a 6-week isolation of males, MR binding capacity was diminished and MR/GR ratio inverted in favor of GR. In addition, fluoxetine induced elevation of cytosolic GR protein level in the pituitary and hypothalamus, the latter change being gender-specific. The results point to gender-related differences in the CRs functioning and suggest that both MR and GR may contribute to well-known sexual dimorphism in vulnerability to stress and stress-related disorders and in the outcome of antidepressant treatment.

Research Highlights► GR and MR binding capacity differs between male and female rat hippocampus. ► Fluoxetine affects hippocampal MR binding activity in a gender-specific manner. ► GR protein level in pituitary cytosol of males is higher than in females. ► Fluoxetine elicited gender-specific changes in pituitary and hipothalamic GR level. ► MR and GR may contribute to sexual dimorphism in response to antidepressants.