Regulation of the gonadotropin-releasing hormone receptor (GnRHR) by RGS proteins: role of the GnRHR carboxyl-terminus

Mol Cell Endocrinol. 2002 Jun 14;191(2):149-56. doi: 10.1016/s0303-7207(02)00082-5.


The cytoplasmic carboxyl-terminus of G-protein coupled receptors (GPCRs), absent in the mammalian gonadotropin-releasing hormone receptor (GnRHR), plays an important role in receptor expression, desensitization, internalization and efficiency of coupling to G proteins. Regulators of G protein signaling (RGS) likewise are involved in regulating GPCR-G protein mediated responses and can regulate transcription of other genes. In this study, we evaluate differential expression, ligand binding and effector coupling of the rat GnRHR (rGnRHR) and a chimera of rGnRHR with the pre-mammalian carboxyl domain (rGnRHR-C-tail). Membrane expression of the chimeric receptor and G(q)alpha and G(s)alpha-mediated signaling was increased 2- and 1.5-fold, respectively by RGS10, while RGS3 did not interfere with rGnRHR and rGnRHR-C-tail cell surface expression in spite of negatively regulating GnRH-stimulated G(q)alpha-mediated signaling by both receptors. The rGnRHR and rGnRHR-C-tail showed similar internalization rates in the presence of either RGS protein, indicating that the modification of rGnRHR expression and regulation in the presence of a carboxyl-terminus by RGS10 was not caused by alteration of the internalization rate. The observations in this study implicate the carboxyl domain of the receptor as a site of interaction for RGS10, but not RGS3. This is the first evidence of an altered cell surface expression and regulation of the GnRHR bearing a carboxyl-terminus by RGS proteins.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Cell Line
  • Gene Expression Regulation / drug effects*
  • Ligands
  • Protein Binding
  • Protein Structure, Tertiary
  • Protein Transport
  • RGS Proteins / genetics
  • RGS Proteins / pharmacology*
  • Rats
  • Receptors, LHRH / chemistry
  • Receptors, LHRH / genetics*
  • Receptors, LHRH / metabolism
  • Recombinant Fusion Proteins
  • Signal Transduction / drug effects
  • Transfection


  • Ligands
  • RGS Proteins
  • Receptors, LHRH
  • Recombinant Fusion Proteins