The Concise Guide to PHARMACOLOGY 2015/16: Nuclear hormone receptors

The Concise Guide to PHARMACOLOGY 2015/16 provides concise overviews of the key properties of over 1750 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. The full contents can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13352/full. Nuclear hormone receptors are one of the eight major pharmacological targets into which the Guide is divided, with the others being: G protein‐coupled receptors, ligand‐gated ion channels, voltage‐gated ion channels, other ion channels, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The Concise Guide is published in landscape format in order to facilitate comparison of related targets. It is a condensed version of material contemporary to late 2015, which is presented in greater detail and constantly updated on the website www.guidetopharmacology.org, superseding data presented in the previous Guides to Receptors & Channels and the Concise Guide to PHARMACOLOGY 2013/14. It is produced in conjunction with NC‐IUPHAR and provides the official IUPHAR classification and nomenclature for human drug targets, where appropriate. It consolidates information previously curated and displayed separately in IUPHAR‐DB and GRAC and provides a permanent, citable, point‐in‐time record that will survive database updates.


1A. Thyroid hormone receptors
Nuclear hormone receptors 1A. Thyroid hormone receptors Overview: Thyroid hormone receptors (TRs, nomenclature as agreed by the NC-IUPHAR Subcommittee on Nuclear Hormone Receptors [41]) are nuclear hormone receptors of the NR1A family, with diverse roles regulating macronutrient metabolism, cognition and cardiovascular homeostasis. TRs are activated by thyroxine (T 4 ) and thyroid hormone (triiodothyronine). Once activated by a ligand, the receptor acts as a transcription factor either as a monomer, homodimer or heterodimer with members of the retinoid X receptor family. NH-3 has been described as an antagonist at TRs with modest selectivity for TRβ [111].

Further Reading
Huang JV et al.

1F. Retinoic acid-related orphans
Nuclear hormone receptors 1F. Retinoic acid-related orphans Overview: Retinoic acid receptor-related orphan receptors (ROR, nomenclature as agreed by the NC-IUPHAR Subcommittee on Nuclear Hormone Receptors [7]) have yet to be assigned a definitive endogenous ligand, although RORα may be synthesized with a 'captured' agonist such as cholesterol [66,67].

2A. Hepatocyte nuclear factor-4 receptors
Nuclear hormone receptors 2A. Hepatocyte nuclear factor-4 receptors Overview: The nomenclature of hepatocyte nuclear factor-4 receptors is agreed by the NC-IUPHAR Subcommittee on Nuclear Hormone Receptors [7]. While linoleic acid has been identified as the endogenous ligand for HNF4α its function remains ambiguous [167].
HNF4γ has yet to be paired with an endogenous ligand.
Forms a heterodimer with TR2.

Further Reading
Benoit G et al.

2F. COUP-TF-like receptors
Nuclear hormone receptors 2F. COUP-TF-like receptors Overview: COUP-TF-like receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Nuclear Hormone Receptors [7]) have yet to be officially paired with an endogenous ligand.

Further Reading
Benoit G et al.  May be activated by DY131 [166]. May be activated by DY131 [166].

Further Reading
Benoit G et al.

4A. Nerve growth factor IB-like receptors
Nuclear hormone receptors 4A. Nerve growth factor IB-like receptors Overview: Nerve growth factor IB-like receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Nuclear Hormone Receptors [7]) have yet to be officially paired with an endogenous ligand.

Nomenclature
Nerve Growth factor IB Nuclear receptor related 1 Neuron-derived orphan receptor 1 Systematic nomenclature NR4A1 NR4A2 NR4A3 Comments An endogenous agonist, cytosporone B, has been described [168], although structural analysis and molecular modelling has not identified a ligand binding site [4,40,154]. --

Further Reading
Benoit

6A. Germ cell nuclear factor receptors
Nuclear hormone receptors 6A. Germ cell nuclear factor receptors Overview: Germ cell nuclear factor receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Nuclear Hormone Receptors [7]) have yet to be officially paired with an endogenous ligand.    [84,120], the principal signalling cascade appears to involve binding of the activated receptors to nuclear hormone response elements of the genome, with a 15nucleotide consensus sequence AGAACAnnnTGTTCT (i.e. an inverted palindrome) as homo-or heterodimers. They also affect transcription by protein-protein interactions with other transcription factors, such as activator protein 1 (AP-1) and nuclear factor B (NF-B). Splice variants of each of these receptors can form functional or non-functional monomers that can dimerize to form functional or non-functional receptors. For example, alternative splicing of PR mRNA produces A and B monomers that combine to produce functional AA, AB and BB receptors with distinct characteristics [150].

3A. Estrogen receptors
Nuclear hormone receptors Steroid hormone receptors 3A. Estrogen receptors Overview: Estrogen receptor (ER) activity regulates diverse physiological processes via transcriptional modulation of target genes. The selection of target genes and the magnitude of the response, be it induction or repression, are determined by many factors, including the effect of the hormone ligand and DNA binding on ER structural conformation, and the local cellular regulatory environment. The cellular environment defines the specific complement of DNA enhancer and promoter elements present and the availability of coregulators to form functional transcription complexes. Together, these determinants control the resulting biological response.  [ 3 H]dexamethasone also binds to MRin vitro. PR antagonists have been suggested to subdivide into Type I (e.g. onapristone) and Type II (e.g. ZK112993) groups. These groups appear to promote binding of PR to DNA with different efficacies and evoke distinct conformational changes in the receptor, leading to a transcription-neutral complex [43,83]. Mutations in AR underlie testicular feminization and androgen insensibility syndromes, spinal and bulbar muscular atrophy (Kennedy's disease).