Molecular genetics of the stress-responsive adrenocortical axis

Stress-responsive adrenocortical function is the final physiological response to the cascade of events that occurs when the interaction between individuals and their environment takes place. Glucocorticoids are produced in response to perturbance of homeostasis and are necessary for the energy required to restore this homeostasis. Genetics contributes to the individual variation in basal and stimulated plasma glucocorticoid levels and also to adrenal gland mass that increases in response to prolonged adrenal stimulation. This review briefly describes regulation of the adrenocortical axis, summarizes the linkage studies carried out so far in humans and in model organisms, and discusses the potential candidate genes that might contribute to the variation. The significance of individual variations in the glucocorticoid stress-responsiveness, with particular attention to their potential role in the recent explosion of obesity and the prevalence of metabolic syndrome X, is commented upon.