Hypothalamic-pituitary-adrenal axis (HPA axis) (HPA axis)

The hypothalamic-pituitary-adrenal (HPA) axis is a fundamental neuroendocrine system responsible for the body's response to stress and the maintenance of various homeostatic functions, including metabolism and immune response [1][2]. It operates through a cascade involving the release of corticotropin-releasing hormone (CRH) from the hypothalamus, which stimulates the secretion of adrenocorticotropic hormone (ACTH) from the anterior pituitary, ultimately leading to cortisol production by the adrenal cortex [1]. Inhibition of this axis is a primary pharmacological effect of exogenous glucocorticoids, which exert negative feedback on the hypothalamus and pituitary [4]. While therapeutic inhibition is necessary for treating conditions like Cushing's syndrome or congenital adrenal hyperplasia, prolonged suppression can result in secondary adrenal insufficiency and a diminished capacity to respond to physiological stress [3][5]. Consequently, monitoring HPA axis function through cortisol and ACTH levels is vital in clinical practice to prevent life-threatening complications such as adrenal crisis [5].

Other names

HPA axisHTPA axisStress axisHypothalamic-pituitary-adrenal system

Negative feedback regulation via glucocorticoid receptors, inhibition of steroidogenic enzymes (e.g., 11-beta-hydroxylase), and antagonism of glucocorticoid or CRH receptors [1][3][4].