Abrahám I M, Herbison A E
Laboratory of Neuroendocrinology, The Babraham Institute, Cambridge CB2 4AT, UK.
Neuroscience. 2005;131(4):945-51. doi: 10.1016/j.neuroscience.2004.10.046.
Rapid effects of estrogen have now been identified throughout the brain but the extent to which these actions may be different in males and females is unknown. Previous work has shown that estrogen rapidly phosphorylates Ser133 of cAMP responsive element binding protein (CREB) through a non-genomic mechanism. Using this indicator, we have examined here whether non-genomic estrogen actions occur in a sexually dimorphic manner within the adult brain. Male and female mice were gonadectomized and 3 weeks later treated with 17-beta-estradiol or vehicle for 1 h prior to perfusion fixation and subsequent CREB and phosphorylated CREB (pCREB) immunostaining of brain sections. The numbers of cells expressing CREB immunoreactivity were not altered by estrogen treatment or different in males and females in any of the brain regions examined. However, estrogen treatment significantly (P<0.05) increased pCREB-immunoreactive cell numbers in the medial preoptic area, ventrolateral division of the ventromedial nucleus, medial septum and CA1 region of the hippocampus of female mice. In contrast, estrogen increased pCREB levels in the medial septum and CA1 but not in the preoptic area or ventromedial nucleus of male mice. To evaluate the extent to which non-genomic estrogen actions may be sexually differentiated within a single neuronal phenotype, dual labeling immunocytochemistry was undertaken to evaluate the gonadotropin-releasing hormone (GnRH) neuronal phenotype. Estrogen significantly (P<0.05) increased the numbers of GnRH neurons expressing pCREB in female but not male mice. Together, these results demonstrate the existence of a marked sex difference in estrogen's non-genomic effects upon brain function in vivo.
雌激素的快速作用现已在整个大脑中得到确认，但这些作用在雄性和雌性中可能存在的差异程度尚不清楚。先前的研究表明，雌激素通过非基因组机制迅速使环磷酸腺苷反应元件结合蛋白（CREB）的Ser133位点磷酸化。利用这一指标，我们在此研究了非基因组雌激素作用在成年大脑中是否以性别二态性方式发生。对雄性和雌性小鼠进行去势手术，3周后在灌注固定前1小时用17-β-雌二醇或溶剂处理，随后对脑切片进行CREB和磷酸化CREB（pCREB）免疫染色。雌激素处理并未改变表达CREB免疫反应性的细胞数量，在所检查的任何脑区中，雄性和雌性之间也没有差异。然而，雌激素处理显著（P<0.05）增加了雌性小鼠视前内侧区、腹内侧核腹外侧部、内侧隔和海马CA1区中pCREB免疫反应性细胞的数量。相比之下，雌激素增加了雄性小鼠内侧隔和CA1区的pCREB水平，但在视前区或腹内侧核中未增加。为了评估非基因组雌激素作用在单一神经元表型中可能存在的性别差异程度，进行了双重标记免疫细胞化学以评估促性腺激素释放激素（GnRH）神经元表型。雌激素显著（P<0.05）增加了雌性小鼠中表达pCREB的GnRH神经元数量，而雄性小鼠中未增加。总之，这些结果表明雌激素对体内脑功能的非基因组作用存在明显的性别差异。
