Department of Neurobiology and Anatomy, Kochi Medical School, Kochi University, Kohasu, Nankoku, Japan.
J Neuroendocrinol. 2012 Feb;24(2):310-8. doi: 10.1111/j.1365-2826.2011.02231.x.
Oestrogen has important roles not only in the regulation of reproductive function, but also with respect to other functions, such as cognition, emotion and cardiovascular regulation. Oestrogen acts mainly via its oestrogen receptor (ER), namely, ERα and ERβ in target tissues, including the brain. During ageing, the actions of oestrogen are altered in both females and males, raising the possibility that the expression level of ER may be altered with age. Age-related changes in ER expression in female rat brain have been well demonstrated with regard to reproductive ageing, whereas very little is known about the effects of age on the expression of ERs, especially ERβ, in males. In the present study, which aimed to elucidate the effects of ageing on ERβ expression in the male brain at the transcriptional level, we performed in situ hybridisation using young (10weeks), middle-aged (12months) and old (24 months) gonadally-intact male rats. We revealed a wide distribution of ERβ mRNA-positive cells throughout the brain, and found that the number of ERβ mRNA-positive cells was reduced in several brain regions in males with ageing. ERβ mRNA-positive cells were decreased with age in layer 6 of the cerebral cortex, hippocampal CA1/CA3 regions, the dorsal endopiriform nucleus, the medial septal nucleus, various subregions of the amygdala (central, lateral, anterior cortical and posterolateral cortical subnuclei), the anteroventral periventricular nucleus, the substantia nigra pars compacta, the raphe magnus nucleus and the locus coeruleus. These results suggest that ERβ expression in male rat brain decreases with age at the transcriptional level and that these ageing effects are region-specific.
雌激素不仅在生殖功能的调节中起着重要作用,而且对认知、情绪和心血管调节等其他功能也起着重要作用。雌激素主要通过其雌激素受体(ER),即靶组织中的 ERα 和 ERβ 起作用,包括大脑。随着年龄的增长,女性和男性的雌激素作用都会发生改变,这使得 ER 的表达水平可能会随着年龄的增长而改变。关于生殖衰老,已经充分证明了雌性大鼠大脑中 ER 表达随年龄的变化,而关于年龄对雄性 ER 表达(尤其是 ERβ)的影响知之甚少。在本研究中,我们旨在阐明年龄对雄性大脑中 ERβ 转录水平表达的影响,使用年轻(10 周)、中年(12 个月)和老年(24 个月)去势雄性大鼠进行原位杂交。我们揭示了 ERβ mRNA 阳性细胞在大脑中的广泛分布,并发现随着年龄的增长,雄性大脑中几个脑区的 ERβ mRNA 阳性细胞数量减少。在大脑皮层 6 层、海马 CA1/CA3 区、背内嗅核、中隔核、杏仁核的各个亚区(中央、外侧、前皮质和后外侧皮质亚核)、前腹侧室周核、黑质致密部、中缝大核和蓝斑中,ERβ mRNA 阳性细胞随年龄减少。这些结果表明,雄性大鼠大脑中 ERβ 的表达随年龄的增长而在转录水平上下降,并且这些衰老效应具有区域特异性。