Recent advances in the TR2 and TR4 orphan receptors of the nuclear receptor superfamily

J Steroid Biochem Mol Biol. 2002 Aug;81(4-5):291-308. doi: 10.1016/s0960-0760(02)00118-8.


The human testicular receptor 2 (TR2) and TR4 orphan receptors are two evolutionarily related proteins belonging to the nuclear receptor superfamily. Numerous TR2 and TR4 variants and homologs have been identified from different species, including vertebrates (e.g. human, murine, rabbit, fish, and amphibian) and invertebrates (e.g. Drosophila, sea urchin, and nematode) since TR2 was initially isolated over a decade ago. Specific tissue distribution, genomic organization, and chromosomal assignment of both orphan receptors have been investigated. In order to reveal the physiological functions played by both TR2 and TR4, upstream modulators of TR2 and TR4 gene expression, their downstream target gene regulation, feedback mechanisms, and differential modulation mediated by the recruitment of other nuclear receptors and coregulators have been investigated. Studies summarized in the present report have provided unexpected insights into the TR2 and TR4 functions in a variety of biological processes. The essential and difficult tasks of identifying orphan receptor ligands, agonist/antagonist assignment, their physiological functions, and mechanisms of action will continue to challenge nuclear receptor researchers in the future.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation
  • Humans
  • Male
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism*
  • Nuclear Receptor Subfamily 2, Group C, Member 1
  • Receptors, Steroid / chemistry
  • Receptors, Steroid / metabolism*
  • Receptors, Thyroid Hormone / chemistry
  • Receptors, Thyroid Hormone / metabolism*
  • Signal Transduction


  • DNA-Binding Proteins
  • NR2C1 protein, human
  • NR2C2 protein, human
  • Nuclear Proteins
  • Nuclear Receptor Subfamily 2, Group C, Member 1
  • Receptors, Steroid
  • Receptors, Thyroid Hormone