Fast glucocorticoid actions on brain: Back to the future

Rapid, non-transcriptionally mediated, effects of glucocorticoids affect many behaviors as well as inhibition of function in the hypothalamo-pituitary-adrenal axis. In this short review, it is argued that the fast glucocorticoid actions which are mediated by membrane receptors are an ancient type of sterol/steroid-mediated effect, and that these may be the primordial glucocorticoid receptors. Although the fast feedback actions of the glucocorticoids enjoyed study in the middle of the last century, new results and the availability of new techniques suggest that it is again time for a concerted effort to be made to understand the mechanism(s) of these rapid effects.