Glucocorticoid sensitivity in humans

In clinical practice we measure cortisol in plasma and urine and treat disorders of cortisol secretion. In research, extensive studies have dissected the factors that influence the hypothalamic-pituitary-adrenal axis and modulate cortisol secretion. In recent years, however, the research focus has turned toward factors influencing tissue sensitivity to cortisol, both in sites responsible for negative feedback and in peripheral tissues. Key observations include the cloning of glucocorticoid and mineralocorticoid receptors, dissection of their signaling pathways, and recognition of the importance of cortisol metabolism in modulating tissue sensitivity. This article reviews recent data that illustrate the extent to which these research findings are now being applied in clinical practice, addresses the question of whether intrinsic sensitivity to glucocorticoids varies between individuals, and emphasizes the important impact on health and on responsiveness to glucocorticoid therapy.