Bennett Haley L, Gustafsson Jan Ake, Keast Janet R
Prince of Wales Medical Research Institute, University of New South Wales, NSW 2052, Sydney, Australia.
Auton Neurosci. 2003 May 30;105(2):90-100. doi: 10.1016/S1566-0702(03)00044-4.
We have investigated whether bladder afferent neurons are likely to be targets for circulating estrogens by mapping estrogen receptor (ER) distribution in lumbosacral dorsal root ganglia (DRG) of adult female rats. Sensory neurons innervating either the detrusor or trigone regions were identified by application of fluorescent retrograde tracer dyes to the bladder wall. Labelled neurons were classified by their immunoreactivity for either type of ER (ERalpha or ERbeta) and further compared with subpopulations of neurons containing substance P, calcitonin gene-related peptide and vanilloid receptor (a marker of polymodal nociceptors). Both ER types were expressed in numerous sensory neurons of either upper lumbar (L1/L2) or lower lumbar/sacral (L6/S1) ganglia and there was almost complete coexpression of ERalpha and ERbeta. ER-positive neurons were mainly small-medium size (18-25-microm diameter), indicating that they may be nociceptors and/or supply visceral targets. Most bladder-projecting neurons expressed ERs and the majority of these also expressed neuropeptides or vanilloid receptor. Afferent neurons supplying detrusor and trigone regions had similar immunohistochemical features. About a third of the bladder-projecting neurons expressed both ER and vanilloid receptor, suggesting a mechanism by which estrogens could influence bladder pain. The prevalence of different chemical classes of ER-positive bladder-projecting neurons was reflected throughout the entire population of neurons in dorsal root ganglia of these spinal levels, suggesting that neurons supplying other pelvic visceral targets may have similar chemical profiles. These results suggest that many functional classes of sensory neurons innervating the lower urinary tract are likely to be targets for circulating estrogens, including many nociceptor neurons. The coexistence of ERalpha and ERbeta suggests a broad range of potential mechanisms by which estrogens may exert their genomic effects in this system.
我们通过绘制成年雌性大鼠腰骶部背根神经节（DRG）中雌激素受体（ER）的分布图，研究了膀胱传入神经元是否可能是循环雌激素的作用靶点。通过将荧光逆行示踪染料应用于膀胱壁，识别出支配逼尿肌或三角区的感觉神经元。根据神经元对两种ER类型（ERα或ERβ）的免疫反应性对标记的神经元进行分类，并进一步与含有P物质、降钙素基因相关肽和香草酸受体（多模式伤害感受器的标志物）的神经元亚群进行比较。两种ER类型均在腰上部（L1/L2）或腰下部/骶部（L6/S1）神经节的众多感觉神经元中表达，并且ERα和ERβ几乎完全共表达。ER阳性神经元主要为中小尺寸（直径18 - 25微米），表明它们可能是伤害感受器和/或供应内脏靶点。大多数投射至膀胱的神经元表达ER，其中大多数还表达神经肽或香草酸受体。供应逼尿肌和三角区的传入神经元具有相似的免疫组织化学特征。约三分之一投射至膀胱的神经元同时表达ER和香草酸受体，提示雌激素可能影响膀胱疼痛的一种机制。这些脊髓节段背根神经节中整个神经元群体都反映了不同化学类别ER阳性投射至膀胱神经元的普遍性，表明供应其他盆腔内脏靶点的神经元可能具有相似的化学特征。这些结果表明，支配下尿路的许多功能类别的感觉神经元可能是循环雌激素的作用靶点，包括许多伤害感受神经元。ERα和ERβ的共存提示了雌激素可能在该系统中发挥其基因组效应的广泛潜在机制。
