Corticotropin-releasing hormone (CRH) is released from the hypothalamus and controls the secretion of adrenocorticotrophic hormone (ACTH) which acts on the adrenal gland to biosynthesize cortisol. This neuroendocrine system is called the hypothalamic-pituitary-adrenal (HPA) axis.
Cortisone is produced by the action of the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which operates in tissues such as the kidney.
In metabolically important tissues such as adipose and liver, cortisol can also be reactivated from inert cortisone by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). This activity increases local, biologically active cortisol concentrations.
