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

# Nuclear receptors

Fat-soluble hormones (steroids, thyroid hormone, vitamin D, retinoic acid) enter the cell and activate receptors that switch genes on or off.

Updated 2026-11-01

## Key facts

- They are ligand-activated transcription factors, with a DNA-binding domain of two zinc fingers and a hormone-binding domain.
- Type I (glucocorticoid, mineralocorticoid, androgen, oestrogen, progesterone): they wait in the cytoplasm bound to HSP90 and travel to the nucleus with the hormone.
- Type II (thyroid hormone, vitamin D, retinoic acid, PPAR): they already sit on DNA as heterodimers with RXR, and the hormone swaps corepressors for coactivators.
- Their effect takes hours because new RNA and protein must be made.

## In detail

- In blood these hormones travel bound to proteins (cortisol-binding globulin, sex hormone-binding globulin, thyroxine-binding globulin, albumin); only the free fraction enters the cell.
- The hormone crosses the membrane and binds the ligand-binding domain; the receptor changes shape and exposes the AF-2 surface, where coactivators bind.
- The receptor binds hormone response elements in DNA, usually repeated six-base sequences.
- Coactivators acetylate histones and open chromatin; corepressors do the opposite.
- The glucocorticoid receptor also represses inflammation genes by sequestering factors such as NF-κB and AP-1: the basis of its anti-inflammatory effects.

**Also called**
Intracellular hormone receptors

## Clinical notes

- Drugs acting here: dexamethasone and prednisone (glucocorticoid), spironolactone (mineralocorticoid), tamoxifen (oestrogen), fibrates (PPARα) and thiazolidinediones (PPARγ).
- Androgen insensitivity (faulty androgen receptor) gives a female phenotype with a 46,XY karyotype.
- Vitamin D receptor mutations cause vitamin D-dependent rickets type 2, with high calcitriol.
- Oestrogens raise thyroxine-binding globulin: total T4 rises while free T4 stays the same.

## Related conditions

- [Breast cancer](https://durgical.com/en/conditions/breast-cancer/)
- [Rickets and osteomalacia](https://durgical.com/en/conditions/rickets-and-osteomalacia/)
- [Hypothyroidism](https://durgical.com/en/conditions/hypothyroidism/)
- [Cushing syndrome](https://durgical.com/en/conditions/cushing-syndrome/)

## Related

- [Cortisol](https://durgical.com/en/biochemistry/molecules/cortisol/)
- [Aldosterone](https://durgical.com/en/biochemistry/molecules/aldosterone/)
- [Triiodothyronine (T3)](https://durgical.com/en/biochemistry/molecules/triiodothyronine/)
- [Vitamin D (calcitriol)](https://durgical.com/en/biochemistry/molecules/vitamin-d/)
- [Vitamin A (retinol)](https://durgical.com/en/biochemistry/molecules/vitamin-a/)
- [Steroid hormone synthesis (overview)](https://durgical.com/en/biochemistry/topics/steroid-hormone-synthesis/)
- [Hormone classes and mechanisms](https://durgical.com/en/biochemistry/topics/hormone-classes-and-mechanisms/)
- [G protein-coupled receptors and cAMP](https://durgical.com/en/biochemistry/topics/g-protein-coupled-receptors-and-camp/)

## Test yourself

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

## Where is the glucocorticoid receptor before it binds the hormone?

In the cytoplasm, bound to heat-shock proteins (HSP90); with the hormone it is released and enters the nucleus.

## With which receptor do the thyroid and vitamin D receptors form heterodimers?

With the retinoid X receptor (RXR).

## Why do steroid effects take hours?

Because they act by changing gene transcription, and making new RNA and proteins takes time.

## Which structural motif does a nuclear receptor's DNA-binding domain use?

Two zinc fingers, which recognise the hormone response element.

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

Sources: [NR3C1: Glucocorticoid receptor (human)](https://www.uniprot.org/uniprotkb/P04150/entry) (UniProt, 2026); [THRB: Thyroid hormone receptor beta (human)](https://www.uniprot.org/uniprotkb/P10828/entry) (UniProt, 2026); [3GWS: Crystal Structure of T3-Bound Thyroid Hormone Receptor](https://www.rcsb.org/structure/3GWS) (RCSB Protein Data Bank, 2026); [1M2Z: Crystal structure of a dimer complex of the human glucocorticoid receptor ligand-binding domain bound to dexamethasone and a TIF2 coactivator motif](https://www.rcsb.org/structure/1M2Z) (RCSB Protein Data Bank, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

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