Adrenocortical steroids and the brain.
Adrenocortical steroids and the brain.
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肾上腺皮质类固醇和大脑。
DOI：
10.1146/annurev.ph.49.030187.002145
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发表时间：
1987
影响因子：
18.2
通讯作者：
K. Sheppard
中科院分区：
文献类型：
--
作者：
J. Funder;K. Sheppard
综上所述，肾上腺类固醇对大脑的各种影响已被报道，并已于最近进行了详尽的综述。然而，从内分泌生理学的角度来看，人们经常忘记的是，肾上腺皮质的两种独特产物--盐皮质激素和糖皮质激素--在信号水平上的巨大差异。皮质醇或皮质酮的水平比醛固酮高2-3个数量级，这一差异可能被糖皮质激素与血浆蛋白更高的结合而缓和了一个数量级。因此，对于低强度信号的信号检测机制，即盐皮质激素受体，必须具有强大的特异性赋予机制，使其能够识别、结合和响应醛固酮。一些实验室的体外研究表明，I型受体在经典的盐皮质激素靶组织(肾脏、腮腺、肠道)和非靶组织(垂体腺、海马体)中都无法区分醛固酮和皮质酮。这一发现突出了肾脏(Na+转运)或大脑(Na+食欲)中的醛固酮选择性问题。相比之下，体内研究表明，成年和10日龄(微量转皮质素)大鼠的肾脏、结肠、腮腺和脑垂体(但不是在海马体)对皮质酮的摄取和/或保留很少，而醛固酮被所有组织很好地摄取和/或保留，这是体内组织特异性醛固酮选择性的证据。提出了两个非排他性的(即可能是相加的)模型，一个是“前结合”，另一个是“后结合”。这两个模型都符合体外细胞溶胶制剂的非选择性的实验结果，以及体内受体和效应器研究中所看到的严格的特异性。在任何真正意义上，肾上腺类固醇对大脑的作用在很大程度上仍然是一个没有联系的现象学领域，尽管在过去20年里，许多有才华的个人和团体做出了努力。如果没有对现象的描述，即使是最基本的消融和置换类型，我们也没有机会做出生理陈述。在试图建立一个连贯的生理学的过程中，同样重要的是建立一个假说的脚手架，这个假说可以对照现有的实验结果进行检验，并可以用来建议按照逻辑顺序进行进一步的研究。这些假设本身，以及用来实现它们的模型，可能会在接下来的几年里被这些研究证实、修改或拒绝。
In summary, a wide variety of effects of adrenal steroids on the brain have been reported and have been recently and exhaustively reviewed. From the viewpoint of endocrine physiology, however, what is often forgotten is the extraordinary difference in signal level between the two unique products of the adrenal cortex, the mineralocorticoid and glucocorticoid hormones. Levels of cortisol or corticosterone are 2-3 orders of magnitude higher than those of aldosterone, a difference that is tempered by perhaps one order of magnitude by the much higher binding of glucocorticoids to plasma protein. The signal-detecting mechanisms for the lower-intensity signal, i.e. the mineralocorticoid receptor, must therefore have powerful specificity-conferring mechanisms to enable it to recognize, bind, and respond to aldosterone. In vitro studies from a number of laboratories have shown that Type I receptors, in both classic mineralocorticoid target tissues (kidney, parotid, gut) and nontarget tissues (pituitary, hippocampus), cannot distinguish between aldosterone and corticosterone. This finding highlights the problem of aldosterone-selectivity in the kidney (Na+ transport) or the brain (Na+ appetite). In vivo studies, in contrast, show that corticosterone is very poorly taken up and/or retained in kidney, colon, parotid, and pituitary (but not in hippocampus) in mature and 10-day-old (minimal transcortin) rats, whereas aldosterone is well taken up and/or retained by all tissues, evidence for tissue-specific aldosterone selectivity in vivo. Two nonexclusive (i.e. possibly additive) models for such aldosterone selectivity are proposed, one "prebinding" and the other "postbinding". Both models accommodate the experimental findings of the nonselectivity of cytosol preparations in vitro and the stringent specificity seen in in vivo receptor and effector studies. In any real sense, the action of adrenal steroids on the brain is still largely an area of unconnected phenomenology, despite the efforts of a number of talented individuals and groups over the past two decades. Without descriptions of phenomena, even of the most basic ablation and replacement type, we have no chance of making physiological statements. It is equally important, in the attempt to make a coherent physiology, to erect a scaffolding of hypothesis that can be tested against the existing experimental findings and that can serve to suggest further studies in a logical sequence. These hypotheses themselves, and the models used to reify them, may be validated, altered, or rejected by the studies over the next few years.(ABSTRACT TRUNCATED AT 400 WORDS)
影响因子：
56.9
作者：
GREENE, GL;GILNA, P;SHINE, J
通讯作者：
SHINE, J