Glucocorticoids and the HPA axis

Abstract

The glucocorticoids, cortisol and/or corticosterone depending on the species, are steroid hormones produced by cells in the zona fasciculata of the adrenal cortex under the influence of the hypothalamo-pituitary complex (Fig. 1). In normal circumstances their serum concentrations are maintained within narrow limits with pronounced excursions occurring only in accord to a circadian rhythm, which is coupled to the sleep-wake cycle, or in response to physical or emotional stress. The stress-induced changes in circulating glucocorticoids are superimposed upon the existing circadian tone and vary in their rate of onset, magnitude and duration according to the nature, duration and intensity of the insult. For example, insulin-induced hypoglycaemia produces a maximal increase in serum glucocorticoid concentration within 20–30 min and this is followed by a rapid decline in glucocorticoid levels. In contrast, the adreno-cortical response to lipopolysaccharide (LPS) emerges only after 1–2 h but usually persists for 24 h or longer. Significant interspecies variations also occur; for example, rats respond very readily to physical stimuli such as cold while humans are particularly sensitive to emotional trauma and pigs show a marked increase in serum cortisol when deprived of food but are relatively unresponsive to many other stimuli (e.g., histamine, cold). Failure to mount an appropriate adrenocortical response to stress is potentially hazardous and indeed disturbances in hypothalamo-pituitary-adrenocortical (HPA) activity are now considered to be a significant contributory factor in the aetiology of various disease processes (see later).