Vida B, Hrabovszky E, Kalamatianos T, Coen C W, Liposits Z, Kalló I
Department of Endocrine Neurobiology, Institute of Experimental Medicine, Budapest, Hungary.
J Neuroendocrinol. 2008 Nov;20(11):1270-7. doi: 10.1111/j.1365-2826.2008.01787.x. Epub 2008 Aug 22.
Oestrogen regulates various aspects of circadian rhythm physiology. The presence of oestrogen receptors within the suprachiasmatic nucleus (SCN), the principal circadian oscillator, indicates that some actions of oestrogen on circadian functions may be exerted at that site. The present study analysed sex differences, topographic distribution, and neurochemical phenotype of neurones expressing the alpha and beta subtypes of oestrogen receptors (ERalpha and ERbeta) in the mouse SCN. We found that relatively few neurones in the SCN are immunoreactive (IR) for ERalpha (approximately 4.5% in females and 3% in males), but five- to six-fold more SCN neurones express ERbeta. ER-IR neurones are primarily in the shell subdivision of the nucleus and show differences between the sexes, significantly greater numbers being found in females. Treatment of male or female gonadectomised mice with oestradiol benzoate for 24 h substantially reduced the number of ERbeta-IR neurones, but not ERalpha-IR neurones. Double-labelling immunocytochemical experiments to characterise the phenotype of the oestrogen-receptive neurones showed the presence of the calcium-binding proteins calretinin or calbindin D28K in approximately 12% and 10%, respectively, of ERalpha-IR neurones. A higher proportion (approximately 38%) of ERbeta-IR neurones contains calbindin D28K; a few (approximately 2%) express calretinin or vasopressin. These double-labelled cells appear primarily in the shell subdivision of the SCN. Neither vasoactive intestinal polypeptide- nor gastrin releasing peptide-immunoreactivity was observed in ER-IR neurones. These data indicate that the primary target cells for oestrogen are in the shell subdivision of the nucleus. The sexually differentiated expression and distribution of ERalpha and ERbeta in various cell populations of the SCN suggest multiple modes of oestrogen signalling within this nucleus, which may modulate circadian functions.
雌激素调节昼夜节律生理学的各个方面。在主要的昼夜节律振荡器视交叉上核（SCN）中存在雌激素受体，这表明雌激素对昼夜节律功能的某些作用可能在该部位发挥。本研究分析了小鼠SCN中表达雌激素受体α和β亚型（ERα和ERβ）的神经元的性别差异、拓扑分布和神经化学表型。我们发现，SCN中相对较少的神经元对ERα呈免疫反应性（IR）（雌性约为4.5%，雄性约为3%），但表达ERβ的SCN神经元数量多五到六倍。ER-IR神经元主要位于核的壳部亚区，且存在性别差异，雌性中的数量明显更多。用苯甲酸雌二醇对雄性或雌性去势小鼠进行24小时处理，可显著减少ERβ-IR神经元的数量，但不会减少ERα-IR神经元的数量。用于表征雌激素受体神经元表型的双重标记免疫细胞化学实验表明，分别约12%和10%的ERα-IR神经元中存在钙结合蛋白钙视网膜蛋白或钙结合蛋白D28K。较高比例（约38%）的ERβ-IR神经元含有钙结合蛋白D28K；少数（约2%）表达钙视网膜蛋白或加压素。这些双重标记的细胞主要出现在SCN的壳部亚区。在ER-IR神经元中未观察到血管活性肠肽或胃泌素释放肽免疫反应性。这些数据表明，雌激素的主要靶细胞位于核的壳部亚区。ERα和ERβ在SCN不同细胞群体中的性别分化表达和分布表明，该核内存在多种雌激素信号传导模式，这可能调节昼夜节律功能。
