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

LHRH Receptors
Gonadotropin-Releasing Hormone
Inositol Phosphates
His(5)-Trp(7)-Tyr(8)-lHRH
Cercopithecus aethiops
Rana catesbeiana

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., ... 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.

GnRH-II analogs for selective activation and inhibition of non-mammalian and type-II mammalian GnRH receptors. / Maiti, Kaushik; Li, Jian Hua; Wang, Ai Fen; Acharjee, Sujata; Kim, Wang Phil; Im, Wook Bin; Kwon, Hyuk Bang; Seong, Jae Young.

In: Molecules and Cells, Vol. 16, No. 2, 01.10.2003, p. 173-179.

Research output: Contribution to journalArticle

Maiti, K, Li, JH, Wang, AF, Acharjee, S, Kim, WP, Im, WB, Kwon, HB & Seong, JY 2003, 'GnRH-II analogs for selective activation and inhibition of non-mammalian and type-II mammalian GnRH receptors', Molecules and Cells, vol. 16, no. 2, pp. 173-179.
Maiti K, Li JH, Wang AF, Acharjee S, Kim WP, Im WB et al. GnRH-II analogs for selective activation and inhibition of non-mammalian and type-II mammalian GnRH receptors. Molecules and Cells. 2003 Oct 1;16(2):173-179.
Maiti, Kaushik ; Li, Jian Hua ; Wang, Ai Fen ; Acharjee, Sujata ; Kim, Wang Phil ; Im, Wook Bin ; Kwon, Hyuk Bang ; Seong, Jae Young. / GnRH-II analogs for selective activation and inhibition of non-mammalian and type-II mammalian GnRH receptors. In: Molecules and Cells. 2003 ; Vol. 16, No. 2. pp. 173-179.
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AU - Seong, Jae Young

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