The hypothalamic-pituitary-adrenal (HPA) axis controls the secretion of adrenocorticotropic hormone (ACTH) from the anterior pituitary [1][2]. The hypothalamus secretes corticotropin-releasing hormone (CRH) which stimulates ACTH release [2][3]. CRH is produced by neurosecretory cells in the paraventricular nucleus (PVN) of the hypothalamus [3][4]. The PVN projects axons to the anterior pituitary, releasing CRH at the median eminence to trigger ACTH secretion into the bloodstream [3][5]. ACTH then stimulates the adrenal cortex to produce cortisol [2][3].

The HPA axis forms a negative feedback loop – cortisol acts back on the hypothalamus and pituitary to suppress CRH and ACTH production [1][6]. Neural regulation of ACTH secretion allows the body to mount the appropriate physiological stress response [4][5]. Disruption of HPA axis signaling can lead to dysregulated cortisol levels and impaired stress responses [3][6].