Nuclear Receptors

Nuclear receptors (also known as nuclear hormone receptors) are a large family of transcription factors that bind directly to DNA to regulate the expression of target genes. They regulate the cellular response to hormones such as sex steroids, vitamin D3, adrenal steroids and other metabolic ligands, and are involved in metabolism, development and reproduction.


The nuclear receptor superfamily is classified by sequence alignment and phylogenetic tree construction into six main subfamilies:

  • Thyroid Hormone Receptor-like: includes thyroid receptor, retinoic acid receptor, PPAR, LXR, FXR, VDR, PXR and CAR
  • Retinoid X Receptor-like: includes RXR
  • Estrogen Receptor-like (also known as steroid hormone receptors): includes receptors for estrogen (ER), androgen, glucocorticoid, mineralocorticoid and progesterone
  • Nerve Growth Factor IB-like
  • Steroidogenic Factor-like
  • Germ Cell Nuclear Factor-like
Regulation and Disease

Of the 48 nuclear receptors in the human genome, 24 are ligand-dependent transcription factors. The activity of endogenous ligands on nuclear receptors is normally to upregulate gene expression. Upon ligand-binding a conformation change results in the receptor that regulates the recruitment of coregulators and chromatin-modifying machinery. The majority of nuclear receptors bind-sequence specific promoter elements on target genes either as monomers, homodimers or heterodimers with RXR.

Nuclear receptors are important mediators of disease in general, with receptor mutations responsible for a range of diseases. Mutations in the androgen receptor can cause infertility and prostate cancer; mutations in PPAR can result in colon cancer and diabetes mellitus; and mutations in the estrogen receptor can cause breast cancer.