Adrenocortical steroids and the brain

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)