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[Biochemistry](https://durgical.com/en/biochemistry/) · Molecule

# Cortisol

The main glucocorticoid: it raises glucose, mobilises reserves in fasting and stress, and damps down inflammation.

Updated 2026-11-01

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## Key facts

- The zona fasciculata makes it under ACTH control; it peaks on waking and dips around midnight.
- In blood it travels mainly bound to cortisol-binding globulin (transcortin) and albumin.
- It induces PEPCK and glucose 6-phosphatase (gluconeogenesis), breaks down muscle protein, helps lipolysis and is permissive for glucagon and catecholamines.
- It acts through the (nuclear) glucocorticoid receptor; in the kidney 11β-HSD2 inactivates it so it does not occupy the mineralocorticoid receptor.

**Also called**
Hydrocortisone

**Formula**
C21H30O5

**PubChem**
[CID 5754](https://pubchem.ncbi.nlm.nih.gov/compound/5754)

## Structure

- A 21-carbon steroid with hydroxyl groups on carbons 11β, 17α and 21 and a ketone on carbons 3 and 20.
- The 11β-hydroxyl is essential: the enzyme 11β-HSD2 oxidises it to form cortisone, which is inactive.

## Clinical notes

- Excess (Cushing syndrome): central obesity, purple striae, hyperglycaemia, hypertension, proximal muscle weakness and osteoporosis.
- Deficiency (adrenal insufficiency): fatigue, hypotension, hypoglycaemia and, in Addison disease, hyperpigmentation from high ACTH.
- Liquorice inhibits 11β-HSD2: cortisol activates the mineralocorticoid receptor and causes hypertension with hypokalaemia.

## Pathways

- [Gluconeogenesis](https://durgical.com/en/biochemistry/pathways/gluconeogenesis/)
- [Adrenal cortisol synthesis](https://durgical.com/en/biochemistry/pathways/adrenal-cortisol-synthesis/)

## Related conditions

- [Cushing syndrome](https://durgical.com/en/conditions/cushing-syndrome/)
- [Adrenal insufficiency](https://durgical.com/en/conditions/adrenal-insufficiency/)
- [Congenital adrenal hyperplasia due to 21-hydroxylase deficiency](https://durgical.com/en/conditions/congenital-adrenal-hyperplasia-due-to-21-hydroxylase-deficiency/)

## Related

- [Adrenal enzymes and congenital adrenal hyperplasia](https://durgical.com/en/biochemistry/topics/adrenal-enzymes-and-congenital-adrenal-hyperplasia/)
- [11β-Hydroxylase (CYP11B1)](https://durgical.com/en/biochemistry/enzymes/11-hydroxylase/)
- [21-Hydroxylase (CYP21A2)](https://durgical.com/en/biochemistry/enzymes/21-hydroxylase/)
- [Steroid hormone synthesis (overview)](https://durgical.com/en/biochemistry/topics/steroid-hormone-synthesis/)
- [Nuclear receptors](https://durgical.com/en/biochemistry/topics/nuclear-receptors/)
- [Catecholamines: synthesis and breakdown](https://durgical.com/en/biochemistry/topics/catecholamines-synthesis-and-breakdown/)
- [Phosphoenolpyruvate carboxykinase (PEPCK)](https://durgical.com/en/biochemistry/enzymes/phosphoenolpyruvate-carboxykinase/)
- [Fed, fasting and starvation states](https://durgical.com/en/biochemistry/topics/fed-fasting-and-starvation-states/)
- [Cholesterol](https://durgical.com/en/biochemistry/molecules/cholesterol/)

## Test yourself

Think of the answer, then tap the question to see it.

## How does cortisol favour gluconeogenesis?

It induces PEPCK and glucose 6-phosphatase transcription and supplies amino acids by breaking down muscle protein.

## Why does cortisol not normally act as a mineralocorticoid in the kidney?

Because 11β-HSD2 turns it into inactive cortisone before it binds the mineralocorticoid receptor.

## At what time of day is cortisol highest?

On waking, early in the morning; the lowest value is around midnight.

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Molecules are shown in their neutral form, as the databases deposit them; in the cell the acids and phosphates are ionised.

Educational information, not medical advice. For any symptom, see a health professional.

Sources: [Cortisol (CID 5754)](https://pubchem.ncbi.nlm.nih.gov/compound/5754) (PubChem, NCBI, 2026) · Public domain; [Cortisol blood test: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/003693.htm) (MedlinePlus, US National Library of Medicine, 2026); [NR3C1: Glucocorticoid receptor (human)](https://www.uniprot.org/uniprotkb/P04150/entry) (UniProt, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

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