GnRH-II analogs for selective activation and inhibition of non-mammalian and type-II mammalian GnRH receptors

Kaushik Maiti, Jian Hua Li, Ai Fen Wang, Sujata Acharjee, Wang Phil Kim, Wook Bin Im, Hyuk Bang Kwon, Jae Young Seong

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Recently, we identified three types of non-mammalian gonadotropin-releasing hormone receptors (GnRHR) in the bullfrog (designated bfGnRHR-1-3), and a mammalian type-II GnRHR in green monkey cell lines (denoted gmGnRHR-2). All these receptors responded better to GnRH-II than GnRH-I, while mammalian type-I GnRHR showed greater sensitivity to GnRH-I than GnRH-II. In the present study, we designed new GnRH-II analogs and examined whether they activated or inhibited non-mammalian and mammalian type-II GnRHRs. [D-Ala6]GnRH-II, with D-Ala substituted for Gly6 in GnRH-II, increased inositol phosphate (IP) production in cells stably expressing non-mammalian GnRHRs more effectively than native GnRH-II. However, it exhibited lower activity for mammalian type-I GnRHR than GnRH-I itself. Trptorelix-1, a GnRH-II antagonist, inhibited GnRH-induced IP production in cells expressing non-mammalian GnRHRs more effectively than Cetrorelix, a GnRH-I antagonist. Trptorelix-1, however, had lower potency for mammalian type-I GnRHR than Cetrorelix. Ligand-receptor binding assays revealed that [D-Ala6]GnRH-II and Trptorelix-1 have higher affinities for non-mammalian GnRHRs but lower affinities for mammalian type-I GnRHR than GnRH-II and Cetrorelix, respectively. Moreover, [D-Ala 6] GnRH-II and Trptorelix-1 had a higher affinity for gmGnRHR-2 than GnRH-II and Cetrorelix, respectively. These results indicate that [D-Ala 6]GnRH-II and Trptorelix-1 are highly effective agonist and antagonist, respectively, for non-mammalian and type-II mammalian GnRHRs.

Original languageEnglish
Pages (from-to)173-179
Number of pages7
JournalMolecules and Cells
Volume16
Issue number2
Publication statusPublished - 2003 Oct 1
Externally publishedYes

    Fingerprint

Keywords

  • GnRH Analogs
  • GnRH-II
  • Ligand Selectivity
  • Non-Mammalian and Mammalian Type-II GnRH Receptor

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Maiti, K., Li, J. H., Wang, A. F., Acharjee, S., Kim, W. P., Im, W. B., Kwon, H. B., & Seong, J. Y. (2003). GnRH-II analogs for selective activation and inhibition of non-mammalian and type-II mammalian GnRH receptors. Molecules and Cells, 16(2), 173-179.