Preferential ligand selectivity of the monkey type-II gonadotropin- releasing hormone (GnRH) receptor for GnRH-2 and its analogs

Ai Fen Wang, Jian Hua Li, Kaushik Maiti, Wang Phil Kim, Hae Mook Kang, Jae Young Seong, Hyuk Bang Kwon

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Gonadotropin-releasing hormone (GnRH) regulates the reproductive system through the cognate GnRH receptor (GnRHR) in vertebrates. In this study, we cloned a cDNA encoding the full-length open reading frame sequence for green monkey type-II GnRHR (gmGnRHR-2) from the genomic DNA of CV-1 cells. Transient transfection study showed that gmGnRHR-2 was able to induce both c-fos promoter- and cAMP responsive element-driven transcriptional activities, indicating that gmGnRHR-2 couples to both Gs- and Gq/11-linked signaling pathways. gmGnRHR-2 responded better to GnRH-2 ([His5, Trp 7, Tyr8]GnRH) than GnRH-1 ([Tyr5, Leu 7, Arg8]GnRH). Substitutions of His5, Trp 7, and/or Tyr8 in GnRH-1 increased the potency to activate gmGnRHR-2, suggesting that individual His5, Trp 7, and Tyr8 in GnRH-2 contributed to differential ligand sensitivity of gmGnRHR-2. Substitution of D-Ala for Gly6 in GnRH-2 increased the potency to activate the receptor, suggesting that GnRH-2 has a constrained conformation when it binds to the receptor. GnRH-induced gmGnRHR-2 activation was specifically inhibited by GnRH-2 antagonists, Trptorelix-1 and -2, but not by a GnRH-1 antagonist, Cetrorelix. In conclusion, gmGnRHR-2 revealed preferential ligand selectivity for GnRH-2 and its analogs, suggesting that gmGnRHR-2 has a functional activity that is different from mammalian type-I GnRHRs but similar to non-mammalian GnRHRs.

Original languageEnglish
Pages (from-to)33-42
Number of pages10
JournalMolecular and Cellular Endocrinology
Volume209
Issue number1-2
DOIs
Publication statusPublished - 2003 Nov 14
Externally publishedYes

Keywords

  • GnRH analogs
  • GnRH-2
  • Ligand selectivity
  • Monkey type-II GnRH receptor

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

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