Sapolsky RM
Department of Biological Sciences Stanford University, Stanford, CA 94305, USA.
Stress. 1997 Oct;2(1):1-12. doi: 10.3109/10253899709014733.
In endless facets of physiology, there are points of homeostatic balance, such that too much or too litttle of something can both be deleterious (i.e., an "inverse U" pattern). This is particularly true when considering glucocorticoids (GCs), the adrenals steroid secreted during stress. In the first part of this paper, I review a number of realms in which a paucity and an excess of GCs are both damaging. Some findings are classical (for example, concerning GC effects upon body weight), while some are quite recent and have considerable implications for both physiology and pathophysiology (for example, inverse U's of GC actions in the realm of immunity and neuronal survival). The second part of the review considers the far thornier issue of how such inverse U's of GC actions are generated on a cellular and molecular level. One solution that has evolved, primarily in the hippocampus within the nervous system, involves the presence of two different types of receptors for GCs within the same cells; so long as the two receptors have very different affinities and mediate opposing effects on some cellular endpoint, an inverse U will emerge. The second solution, found in a number of peripheral tissues, involves GCs having opposing effects on the amount of some signal being generated (e.g., an immune cytokine) and the sensitivity of target tissues to that signal; under conditions that appear to be physiologically relevant, inverse U's emerge from this pattern as well. The final section of this review considers the enormous role played by Bruce McEwen in the emergence of this literature. I suggest that while much of this obviously has to do with the facts that have come from his group, another substantial contribution is from his steadying and supportive personality, the veritable embodiment of homeostatic balance.
在生理学的诸多方面，存在着稳态平衡的关键点，即某物过多或过少都可能有害（即“倒U”模式）。在考虑糖皮质激素（GCs）时尤其如此，它是应激期间分泌的肾上腺类固醇。在本文的第一部分，我回顾了一些GCs缺乏和过量均具有损害性的领域。一些发现是经典的（例如，关于GCs对体重的影响），而一些则是相当新的，对生理学和病理生理学都有重要意义（例如，GCs在免疫和神经元存活领域的作用呈倒U形）。综述的第二部分考虑了在细胞和分子水平上如何产生这种GCs作用的倒U形这一棘手得多的问题。一种主要在神经系统内的海马体中演化出的解决方案涉及同一细胞内存在两种不同类型的GCs受体；只要这两种受体具有非常不同的亲和力并对某些细胞终点产生相反的影响，就会出现倒U形。在许多外周组织中发现的第二种解决方案涉及GCs对某些信号产生量（例如免疫细胞因子）和靶组织对该信号的敏感性具有相反的影响；在看似生理相关的条件下，这种模式也会出现倒U形。本综述的最后一部分考虑了布鲁斯·麦克尤恩在这一文献出现过程中所起的巨大作用。我认为，虽然这其中很多显然与他所在团队得出的事实有关，但另一个重要贡献来自他沉稳且支持他人的个性，这是稳态平衡的真实体现。
