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 · Right adrenal gland
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 glucocorticoidsPattern 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 ↓
Actions by tissue and what excess looks like
| Tissue | Action | In excess (Cushing) |
|---|---|---|
| Liver | ↑ gluconeogenesis and glycogen | Hyperglycemia, diabetes |
| Muscle and skin | ↑ proteolysis; releases amino acids | Proximal myopathy, striae, bruising |
| Adipose tissue | Peripheral lipolysis, central redistribution | Central obesity, round face, dorsal hump |
| Bone | ↓ osteoblasts, ↓ gut Ca²⁺ absorption | Osteoporosis and fractures |
| Immunity | ↓ cytokines, lymphocytes and eosinophils | Infections, poor wound healing |
| Vessels | 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.
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.
See it in 3D
The structures of Durgical's 3D anatomy where it happens.
Related topics
- The HPA axis and its circadian rhythm
- Glucagon and the counter-regulatory hormones
- The endocrine stress response
- Aldosterone: actions and control
- Bone remodeling
Related conditions
In Biochemistry
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 (OpenStax (Rice University), 2022); Hypercortisolism (Cushing Syndrome) (StatPearls (NCBI Bookshelf), 2024); Adrenal Insufficiency (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).
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Representative model, for educational purposes only.