Steroid hormones act via evolutionarily conserved nuclear receptors to regulate neuronal phenotype during development, maturity and disease. Steroid hormones exert 'global' effects in organisms to produce coordinated physiological responses whereas, at the 'local' level, individual neurons can respond to a steroidal signal in highly specific ways. This review focuses on two phenomena-the loss of dendritic processes and the programmed cell death (PCD) of neurons-that can be regulated by steroid hormones (e.g. during sexual differentiation in vertebrates). In insects such as the moth, Manduca sexta, and fruit fly, Drosophila melanogaster, ecdysteroids orchestrate a reorganization of neural circuits during metamorphosis. In Manduca, accessory planta retractor (APR) motoneurons undergo dendritic loss at the end of larval life in response to a rise in 20-hydroxyecdysone (20E). Dendritic regression is associated with a decrease in the strength of monosynaptic inputs, a decrease in the number of contacts from pre-synaptic neurons, and the loss of a behavior mediated by these synapses. The APRs in different abdominal segments undergo segment-specific PCD at pupation and adult emergence that is triggered directly and cell-autonomously by a genomic action of 20E, as demonstrated in cell culture. The post-emergence death of APRs provides a model for steroid-mediated neuroprotection. APR death occurs by autophagy, not apoptosis, and involves caspase activation and the aggregation and ultracondensation of mitochondria. Manduca genes involved in segmental identity, 20E signaling and PCD are being sought by suppressive subtractive hybridization (SSH) and cDNA microarrays. Experiments utilizing Drosophila as a complementary system have been initiated. These insect model systems contribute toward understanding the causes and functional consequences of dendritic loss and neurodegeneration in human neurological disorders.

中文翻译：

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全球化思考，局部行动：类固醇激素对树突结构的调节，突触连接性和单个神经元的死亡。

类固醇激素通过进化上保守的核受体起作用，在发育，成熟和疾病过程中调节神经元表型。类固醇激素在生物体中发挥“整体”作用以产生协调的生理反应，而在“局部”水平上，单个神经元可以以高度特定的方式对类固醇信号作出反应。这项审查集中在两种现象-树突状过程的丧失和神经元的程序性细胞死亡（PCD）-可以由类固醇激素调节（例如在脊椎动物的性分化期间）。在诸如蛾，曼杜卡六倍体和果蝇，果蝇，果蝇等昆虫中，蜕皮类固醇在变态过程中精心安排了神经回路的重组。在曼杜卡 辅助足底牵开器（APR）运动神经元在幼虫寿命结束时响应20-羟基蜕皮激素（20E）的增加而经历树突状丢失。树突退化与单突触输入强度的降低，与突触前神经元的接触次数减少以及这些突触介导的行为丧失有关。如在细胞培养中所示，不同的腹部节段中的APR在化up和成年出苗时经历节段特异性PCD，并通过20E的基因组作用直接和细胞自主触发。APR的芽后死亡为类固醇介导的神经保护提供了一个模型。APR死亡是通过自噬而不是细胞凋亡发生的，并且涉及caspase活化以及线粒体的聚集和超浓缩。Manduca基因参与区段识别，抑制性消减杂交（SSH）和cDNA微阵列正在寻求20E信号和PCD。利用果蝇作为补充系统的实验已经开始。这些昆虫模型系统有助于理解人类神经系统疾病中树突丢失和神经变性的原因和功能后果。