University of Belgrade, Institute for Biological Research "Siniša Stanković," Department of Biochemistry, 142 Despot Stefan Blvd., 11060 Belgrade, Serbia.
Brain Res. 2011 Apr 12;1384:61-8. doi: 10.1016/j.brainres.2011.01.078. Epub 2011 Jan 31.
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.
研究了未接受治疗的雄性与雌性大鼠之间的差异，这些大鼠在接受抗抑郁药氟西汀治疗前后，经历了慢性社会隔离应激，研究了应激前后糖皮质激素受体（GR）和盐皮质激素受体（MR）在垂体、下丘脑、海马和前额皮质中的蛋白水平。结果表明，雄性大鼠的海马细胞质中 GR 和 MR 的激素结合能力以及垂体细胞质中的 GR 蛋白水平均高于雌性大鼠。在两性中，MR 对 GR 的结合都超过了 GR。虽然氟西汀治疗和社会隔离对 GR 活性没有影响，但对 MR 的影响是有性别差异的。氟西汀仅在雌性中促进 MR 激素结合，增加了 MR/GR 活性比。相反，在雄性大鼠隔离 6 周后，MR 的结合能力降低，MR/GR 比值向 GR 倾斜。此外，氟西汀诱导了垂体和下丘脑细胞溶质中 GR 蛋白水平的升高，这种变化是具有性别特异性的。这些结果表明，CR 功能存在性别差异，并表明 MR 和 GR 可能有助于众所周知的应激易感性和应激相关障碍以及抗抑郁治疗结果的性别二态性。
