Joëls M
Department of Experimental Zoology, Kruislaan 320, University of Amsterdam, 1098 SM, Amsterdam, The Netherlands.
Front Neuroendocrinol. 1997 Jan;18(1):2-48. doi: 10.1006/frne.1996.0144.
Adrenocortical and gonadal steroid hormones can pass the blood-brain barrier and bind to intracellular receptors in the brain. In addition to steroid hormones binding to intracellular steroid receptors, metabolites of these steroids and steroid hormones produced in the brain (neurosteroids) are thought to bind to membrane recognition sites. Actions mediated by the intracellular receptors are generally delayed in onset and are of prolonged duration, whereas the hormones binding to membrane recognition sites induce fast effects. Both fast and delayed actions by steroid hormones potentially alter the electrical properties of neuronal membranes and thus the firing patterns of neurons carrying receptors for the hormones. We here review the fast and delayed actions by steroid hormones on single cell electrical properties in the mammalian nervous system. In general, fast effects by corticosteroids-presumably mediated by membrane receptors-induce inhibitory effects on cellular firing, although regional differences seem to exist. Delayed effects by corticosteroid hormones via mineralocorticoid receptors serve to maintain or enhance fast transmission in the brain, while modulatory inputs are suppressed. By contrast, corticosteroids acting through glucocorticoid receptors suppress transmission carried by amino acids, particularly when the activity is elevated in comparison to resting level; modulatory inputs are enhanced. Prolonged activation of glucocorticoid receptors can implicate the integrity of neuronal circuits by allowing considerable influx of calcium ions during depolarization. Of the gonadal hormones, estradiol mainly exerts excitatory actions, in both a rapid and a delayed mode. Progesterone on the other hand is predominantly inhibitory, usually with a short delay in onset. The effect of androgens on neuronal excitability has not yet been studied in great detail. Finally, neurosteroids and A-ring reduced steroids in general induce rapid effects on firing patterns, probably by acting on ligand gated ion channels. The diverse actions of steroid hormones on single cell activity have consequences for the excitability in local circuits in which these cells participate. This is illustrated in this review for two processes that depend on circuit rather than single cell function, i.e., long term potentiation and epilepsy. The diverging character of steroid hormones with regard to the time frame, space, and nature of their effects is also reflected in the functional processes that are linked to the activity of the networks responding to steroids. In this way steroid hormones add an essentially new aspect to the regulation of functional processes in the brain, during physiological conditions but also when networks are implicated during diseases and disorders. Future research on steroid modulation of cellular excitability will gain considerably from attempts to either link the changed excitability to the underlying molecular events or study the effects on cellular activity in close connection with behavioral functions.
肾上腺皮质激素和性腺甾体激素能够穿过血脑屏障，并与脑内的细胞内受体结合。除了甾体激素与细胞内甾体受体结合外，这些甾体激素的代谢产物以及脑内产生的甾体激素（神经甾体）被认为可与膜识别位点结合。由细胞内受体介导的作用通常起效延迟且持续时间较长，而与膜识别位点结合的激素则会诱导快速效应。甾体激素的快速和延迟作用都可能改变神经元膜的电特性，进而改变携带该激素受体的神经元的放电模式。我们在此综述甾体激素对哺乳动物神经系统单细胞电特性的快速和延迟作用。一般来说，皮质类固醇的快速效应——可能是由膜受体介导的——会对细胞放电产生抑制作用，尽管似乎存在区域差异。皮质类固醇激素通过盐皮质激素受体产生的延迟效应有助于维持或增强脑内的快速传递，同时抑制调节性输入。相比之下，通过糖皮质激素受体起作用的皮质类固醇会抑制由氨基酸介导的传递，尤其是当与静息水平相比活动增强时；调节性输入则会增强。糖皮质激素受体的长期激活可能会通过在去极化过程中允许大量钙离子内流而影响神经回路的完整性。在性腺激素中，雌二醇主要以快速和延迟两种方式发挥兴奋作用。另一方面，孕酮主要起抑制作用，通常起效延迟较短。雄激素对神经元兴奋性的影响尚未得到详细研究。最后，神经甾体和一般的A环还原甾体通常会对放电模式产生快速影响，可能是通过作用于配体门控离子通道。甾体激素对单细胞活性的多种作用会影响这些细胞所参与的局部回路的兴奋性。本综述通过两个依赖于回路而非单细胞功能的过程，即长时程增强和癫痫，对此进行了说明。甾体激素在作用的时间框架、空间和性质方面的不同特点也反映在与对甾体作出反应的网络活动相关的功能过程中。这样，甾体激素在生理条件下以及在疾病和紊乱状态下网络受累时，为脑内功能过程的调节增添了一个全新的方面。未来关于甾体对细胞兴奋性调节的研究，通过将改变的兴奋性与潜在分子事件联系起来，或者紧密结合行为功能来研究对细胞活性的影响，将会大有收获。
