The HPA axis feedback network. Diagram of the biochemical feedback network of the HPA axis as modeled in. Physical or mental stress triggers the secretion of corticotropin releasing hormone CRH in the hypothalamus. CRH is transported to the anterior pituitary gland and stimulates the release of the adrenocorticotropic hormone ACTH. ACTH signals to the adrenal gland to secrete cortisol COR. After binding to the glucocorticoid receptor GR in the pituitary, cortisol negatively regulates the production of CRH and ACTH. The homo dimerization introduces a positive feedback loop giving rise to bistable behavior in accordance with hypocortisolism.