Thyrotropin-releasing hormone and its receptors - A hypothesis for binding and receptor activation

Stanislav Engel, Marvin C. Gershengorn

Research output: Contribution to journalReview articlepeer-review

28 Scopus citations

Abstract

Thyrotropin-releasing hormone (TRH), a tripeptide, exerts its biological effects through stimulation of cell-surface receptors, TRH-R, belonging to the superfamily of G protein-coupled receptors (GPCR). Because of the intermediate size of TRH, it is smaller than polypeptide ligands that interact at GPCR ectodomains and larger than biogenic amines, which interact within GPCR transmembrane domains (TMD), the TRH/TRH-R complex probably shares properties of these 2 extremes, representing a unique system to study GPCR/ligand interactions. In this review, we summarize the current knowledge of the structure-activity relationships in the TRH/TRH-R system. Based on experimental data and the structural information acquired from computer simulations, we formulate a working hypothesis to describe the molecular events underlying the processes of TRH binding and TRH-R activation. This hypothesis represents a starting point for understanding the biology of the TRH/TRH-R system on a molecular level and provides a basis for potential design of new potent and selective modulators of TRH-R's activity.

Original languageEnglish
Pages (from-to)410-419
Number of pages10
JournalPharmacology and Therapeutics
Volume113
Issue number2
DOIs
StatePublished - 1 Feb 2007
Externally publishedYes

Keywords

  • Active conformation
  • Agonist
  • GPCR activation
  • Ligand binding
  • Structure-activity relationships
  • TRH receptor

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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