Bingham Brenda, Williamson Martin, Viau Victor
Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
J Comp Neurol. 2006 Dec 20;499(6):911-23. doi: 10.1002/cne.21151.
Activation of the hypothalamic-pituitary-adrenal (HPA) axis is initiated by neurosecretory neurons residing within the medial parvicellular part of the hypothalamic paraventricular nucleus (PVN). Despite the potency by which sex steroids operate on HPA and medial parvocellular responses to stress, previous topographic and phenotypic studies suggest that gonadal steroid hormone receptors are scarcely, if at all, expressed by PVN neurons controlling anterior pituitary corticotropes. Guided by the pattern of retrograde accumulation of fluorogold, we used a direct connectional approach to define the distribution of androgen receptors (AR) and estrogen-beta receptors (ER-beta) within populations of neurosecretory vs. nonneurosecretory neurons in the PVN. Juxtaposition of AR-immunoreactivity (ir) and ER-beta mRNA to the pattern of intravenous fluorogold labeling showed these steroid hormone receptors to be concentrated within portions of the PVN devoid of neurosecretory neurons. Superimposing receptor profiles onto the pattern of spinal retrograde labeling confirmed a selective distribution of AR-ir within autonomic-related cells of the medial parvocellular division, including its dorsal, lateral, and ventral medial components. ER-beta mRNA expression was likewise concentrated within regions accumulating spinal tracer, highest within the ventral aspect of the PVN. These results indicate a direct influence of gonadal hormones on preautonomic effector neurons and remain in keeping with an indirect influence of androgens on adrenocorticotropin-regulating neurons in the PVN.
下丘脑 - 垂体 - 肾上腺(HPA)轴的激活由位于下丘脑室旁核(PVN)内侧小细胞部的神经分泌神经元启动。尽管性类固醇对HPA轴以及内侧小细胞对应激的反应有显著作用,但先前的拓扑学和表型研究表明,控制垂体前叶促肾上腺皮质激素细胞的PVN神经元几乎不表达性腺类固醇激素受体(即便有表达也极为稀少)。以荧光金逆行累积模式为指导,我们采用直接连接法来确定PVN中神经分泌神经元与非神经分泌神经元群体中雄激素受体(AR)和雌激素β受体(ER-β)的分布。将AR免疫反应性(ir)和ER-β mRNA与静脉注射荧光金标记模式并列显示,这些类固醇激素受体集中在PVN中缺乏神经分泌神经元的部分。将受体分布图叠加到脊髓逆行标记模式上,证实了AR-ir在小细胞内侧部自主神经相关细胞内的选择性分布,包括其背侧、外侧和腹内侧成分。ER-β mRNA表达同样集中在积累脊髓示踪剂的区域,在PVN腹侧最高。这些结果表明性腺激素对自主神经前效应神经元有直接影响,并且与雄激素对PVN中促肾上腺皮质激素调节神经元的间接影响相一致。