The adrenal cortex and life.

The template for our understanding of the physiological role of the adrenal cortex was set by Hans Selye, who demonstrated its key involvement in the response to stress, of whatever origin, and who also introduced the terms glucocorticoid and mineralocorticoid. Despite this, from the late 1940s on there was certainly general awareness of the multiple actions of glucocorticoids, including effects on the thymus and immune system, cardiovascular system, water balance, and the CNS. For these reasons, and perhaps because in the early studies of the actions of individual steroids there was less clear-cut difference between them, there was some initial resistance to the use of these terms. Today they are universal and unchallenged. It can be argued that, with respect to the glucocorticoids, this term colours our perception of their physiological importance, and may be misleading. By taking evidence from disease states, emphasis is placed on extreme conditions that do not necessarily reveal normal physiology. In particular, evidence for the role of glucocorticoid regulation of gluconeogenesis and blood glucose in the normal subject or animal is inconclusive. Similarly, while highly plausible theories explaining glucocorticoid actions on inflammation or the immune system as part of normal physiology have been presented, direct evidence to support them is hard to find. Under extreme conditions of chronic stress, the cumulative actions of glucocorticoids on insulin resistance or immunocompromise may indeed seem to be actually damaging. Two well-documented and long recognized situations create huge variation in glucocorticoid secretion. These are the circadian rhythm, and the acute response to mild stress, such as handling, in the rat. Neither of these can be adequately explained by the need for glucocorticoid action, as we currently understand it, particularly on carbohydrate metabolism or on the immune system. Perhaps we should re-examine other targets at the physiological level. At the present time, some of these seem to be out of fashion.