Experimental and computational study of inter- and intra- species specificity of gonadotropins for various gonadotropin receptors

Joseph Aizen; N Kowalsman; M Kobayashi; L Hollander; Y C Sohn; G Yoshizaki; M Y Niv; B Levavi-Sivan

doi:10.1016/j.mce.2012.08.013

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Experimental and computational study of inter- and intra- species specificity of gonadotropins for various gonadotropin receptors

Journal article

Peer reviewed

Experimental and computational study of inter- and intra- species specificity of gonadotropins for various gonadotropin receptors

Joseph Aizen, N Kowalsman, M Kobayashi, L Hollander, Y C Sohn, G Yoshizaki, M Y Niv and B Levavi-Sivan

Molecular and Cellular Endocrinology, Vol.364(1-2), pp.89-100

2012

DOI: https://doi.org/10.1016/j.mce.2012.08.013

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Abstract

FSH

molecular modeling

G-protein-coupled receptor (GPCR)

signal transduction

glycoprotein hormone receptor

The gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and their receptors play critical roles in vertebrate reproduction. In order to study intra- and interspecies ligand promiscuity of gonadotropins, COS-7 cells were transiently transfected with one of the gonadotropin receptor genes, FSHR or LHR, and tested for activation by gonadotropins from representative fish orders: Aquilliformes (eel; e), Salmoniformes (trout; tr), and Perciformes (tilapia; ta), and of mammalian origin: porcine (p), bovine (b) and human (h).The study reveals complex relations between the gonadotropin hormones and their receptors. Each gonadotropin activated its own cognate receptor. However, taLHR was also activated by hCG and eLHR was activated by hFSH, hCG, and trFSH. For FSHR, the only cross-reactivity detected was for hFSHR, which was activated by pFSH and bFSH. These findings are of great interest and applicability in the context of activation of various GTHRs by their ligands and by ligands from other vertebrates. Analysis of the three-dimensional models of the structures highlights the importance of residues outside of the currently established hormone-receptor interface region. In addition, the interface residues in taFSHR and the effect of exon duplication, which causes an insert in the LRR domain, are suggested to affect the interaction and binding of taFSH.

Details

Title: Experimental and computational study of inter- and intra- species specificity of gonadotropins for various gonadotropin receptors
Authors: Joseph Aizen (Author) - Hebrew University of Jerusalem, Israel
N Kowalsman (Author) - Hebrew University of Jerusalem, Israel
M Kobayashi (Author) - International Christian University, Japan
L Hollander (Author) - International Christian University, Japan
Y C Sohn (Author) - Gangneung-Wonju National University, South Korea
G Yoshizaki (Author) - Tokyo University of Marine Science and Technology, Japan
M Y Niv (Author) - Hebrew University of Jerusalem, Israel
B Levavi-Sivan (Author) - Hebrew University of Jerusalem, Israel
Publication details: Molecular and Cellular Endocrinology, Vol.364(1-2), pp.89-100
Publisher: Elsevier Ireland Ltd.
Date published: 2012
DOI: 10.1016/j.mce.2012.08.013
ISSN: 0303-7207
Organisation Unit: University of the Sunshine Coast, Queensland; GeneCology Research Centre - Legacy; Centre for Bioinnovation
Language: English
Record Identifier: 99448974502621
Output Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Web Of Science research areas: Cell Biology; Endocrinology & Metabolism

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