[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Physiology](https://durgical.com/en/physiology/) › [Endocrine](https://durgical.com/en/physiology/#s-endocrine) › Actions of cortisol [Physiology](https://durgical.com/en/physiology/) · [Endocrine](https://durgical.com/en/physiology/#s-endocrine) # Actions of cortisol - Mechanism - Exam priority: high Cortisol is the lasting stress hormone: it raises glucose, damps inflammation and keeps blood pressure up. Updated 2026-11-01 Also called: Glucocorticoids, Endogenous hydrocortisone **See it in 3D:** [Left adrenal gland](https://durgical.com/en/anatomy/suprarenal-gland/) · [Right adrenal gland](https://durgical.com/en/anatomy/suprarenal-gland-abdomen/) ## Key points - It increases hepatic gluconeogenesis and limits glucose uptake by muscle and fat: hyperglycemia and insulin resistance. - Protein breakdown in muscle, skin and bone: proximal weakness, purple striae, thin skin, osteoporosis. - Permissive effect: without cortisol, catecholamines cannot hold blood pressure (refractory hypotension in crisis). - Typical blood count: neutrophilia (demargination) with lymphopenia and eosinopenia. - Normally renal 11β-HSD2 inactivates cortisol; if it is saturated or inhibited (licorice), cortisol acts as a mineralocorticoid. ## What it is Cortisol enters cells and binds the glucocorticoid receptor, which acts as a transcription factor. It mobilizes fuel (glucose from amino acids, fatty acids from fat), damps inflammation and immunity, and lets catecholamines keep vascular tone. Its excess explains the whole Cushing picture; its lack, the hypotension and hypoglycemia of adrenal insufficiency. ## How it works, step by step - About 90% of cortisol circulates bound to transcortin (CBG) and albumin; the free fraction is the active one. - Free cortisol diffuses into the cytoplasm and binds the glucocorticoid receptor, which sheds its chaperones (HSP90). - The complex enters the nucleus and binds glucocorticoid response elements, switching on genes such as PEPCK. - The receptor also blocks NF-κB and AP-1: cytokines, COX-2 and adhesion molecules fall. - It induces annexin A1 (lipocortin), which inhibits phospholipase A2 and the making of prostaglandins and leukotrienes. ### Hormone axes and feedback **Lesion** Adrenal adenoma or exogenous glucocorticoids **Pattern** CRH ↓ · ADH ↓ · ACTH ↓ · Cortisol ↑ #### Primary hyperfunction: Adrenal adenoma or exogenous glucocorticoids **Pattern:** CRH ↓ · ADH ↓ · ACTH ↓ · Cortisol ↑ The gland is autonomous (or the hormone is given): its level rises and negative feedback suppresses the pituitary and hypothalamus. ACTH-independent Cushing: ACTH ↓ (the other adrenal atrophies). Exogenous glucocorticoids are the commonest cause; measured endogenous cortisol may then be low, but the glucocorticoid effect is high. Exam rule: if the pituitary hormone moves opposite to the gland hormone, the problem is in the gland (primary); if they move together, it is central (pituitary or hypothalamus). - Stimulates (+) - Inhibits / negative feedback (−) - Level ↑ - Level ↓ Illustrative schematic drawn by Durgical: simplified axes and classic lab patterns; not for clinical decisions. ## Actions by tissue and what excess looks like | Tissue | Action | In excess (Cushing) | | --- | --- | --- | | [Liver](https://durgical.com/en/conditions/type-2-diabetes-mellitus/) | ↑ gluconeogenesis and glycogen | Hyperglycemia, diabetes | | [Muscle and skin](https://durgical.com/en/conditions/cushing-syndrome/) | ↑ proteolysis; releases amino acids | Proximal myopathy, striae, bruising | | [Adipose tissue](https://durgical.com/en/conditions/cushing-syndrome/) | Peripheral lipolysis, central redistribution | Central obesity, round face, dorsal hump | | [Bone](https://durgical.com/en/conditions/osteoporosis/) | ↓ osteoblasts, ↓ gut Ca²⁺ absorption | Osteoporosis and fractures | | Immunity | ↓ cytokines, lymphocytes and eosinophils | Infections, poor wound healing | | [Vessels](https://durgical.com/en/conditions/arterial-hypertension/) | Permissive for catecholamines and angiotensin II | Hypertension | ## Clinical notes - Cushing syndrome: central obesity, wide purple striae, proximal weakness, hypertension, hyperglycemia and osteoporosis. - Adrenal insufficiency: fatigue, weight loss, fasting hypoglycemia and hypotension; under stress it can progress to shock. - Long-term therapeutic glucocorticoids reproduce the effects of excess, including suppression of the axis. ## Memory aid Cortisol "raids the pantry": it empties muscle, bone and skin to fill the blood with glucose. ## Test yourself Think of the answer, then tap the question to see it. ## Why does a patient with Cushing syndrome struggle to climb stairs? Excess cortisol breaks down muscle protein to feed amino acids to gluconeogenesis; the myopathy hits mainly the proximal hip and shoulder muscles. ## Why does adrenal crisis cause hypotension that does not improve with vasopressors alone? Cortisol is permissive: it maintains adrenergic receptors and the vascular smooth muscle response. Without it, catecholamines lose their effect. ## Why do glucocorticoids cause eosinopenia and lymphopenia but neutrophilia? They redistribute and kill lymphocytes and eosinophils, while releasing neutrophils from the marrow and the vessel wall (demargination). ## Why doesn't cortisol normally act as a mineralocorticoid in the kidney if it binds the same receptor? 11β-HSD2 in the principal cell turns it into inactive cortisone. If the enzyme is saturated (very high cortisol) or inhibited (licorice), cortisol activates the mineralocorticoid receptor. [Add to my cards (4)](https://durgical.app/estudiar/?add=/en/physiology/actions-of-cortisol/) ## See it in 3D The structures of Durgical's 3D anatomy where it happens. - [Left adrenal gland](https://durgical.com/en/anatomy/suprarenal-gland/) - [Right adrenal gland](https://durgical.com/en/anatomy/suprarenal-gland-abdomen/) ## Related topics - [The HPA axis and its circadian rhythm](https://durgical.com/en/physiology/the-hpa-axis-and-its-circadian-rhythm/) - [Glucagon and the counter-regulatory hormones](https://durgical.com/en/physiology/glucagon-and-the-counter-regulatory-hormones/) - [The endocrine stress response](https://durgical.com/en/physiology/the-endocrine-stress-response/) - [Aldosterone: actions and control](https://durgical.com/en/physiology/aldosterone-actions-and-control/) - [Bone remodeling](https://durgical.com/en/physiology/bone-remodeling/) ## Related conditions - [Cushing syndrome](https://durgical.com/en/conditions/cushing-syndrome/) - [Adrenal insufficiency](https://durgical.com/en/conditions/adrenal-insufficiency/) - [Osteoporosis](https://durgical.com/en/conditions/osteoporosis/) - [Type 2 diabetes mellitus](https://durgical.com/en/conditions/type-2-diabetes-mellitus/) ## In Biochemistry - [Cortisol](https://durgical.com/en/biochemistry/molecules/cortisol/) - [Gluconeogenesis](https://durgical.com/en/biochemistry/pathways/gluconeogenesis/) - [Nuclear receptors](https://durgical.com/en/biochemistry/topics/nuclear-receptors/) [← All of physiology](https://durgical.com/en/physiology/) Educational physiology content; not a diagnostic or treatment guide and no substitute for a health professional's advice. Values are approximate references. No doses are given. Sources: [17.6 The Adrenal Glands](https://openstax.org/books/anatomy-and-physiology-2e/pages/17-6-the-adrenal-glands) (OpenStax (Rice University), 2022); [Hypercortisolism (Cushing Syndrome)](https://www.ncbi.nlm.nih.gov/books/NBK551526/) (StatPearls (NCBI Bookshelf), 2024); [Adrenal Insufficiency](https://www.ncbi.nlm.nih.gov/books/NBK441832/) (StatPearls (NCBI Bookshelf), 2024); Hall JE. Guyton and Hall Textbook of Medical Physiology, 13th ed. (ch. 78). Reference book used to check facts; its text and figures are not reproduced (Elsevier, 2016). ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/physiology/actions-of-cortisol/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/physiology/actions-of-cortisol/