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

Joseph Aizen, Noga Kowalsman, Makito Kobayashi, Lian Hollander, Young Chang Sohn, Goro Yoshizaki, Masha Y. Niv, Berta Levavi-Sivan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

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.

Original languageAmerican English
Pages (from-to)89-100
Number of pages12
JournalMolecular and Cellular Endocrinology
Volume364
Issue number1-2
DOIs
StatePublished - 25 Nov 2012

Bibliographical note

Funding Information:
We would like to thank Dr. Y. Kazeto ( Division of Marine Life Sciences, Research Faculty of Fisheries Science, Hokkaido University, Japan ) for the sequence of the Japanese eel LH and FSH receptors, and to Dr. T. Gudermann ( Walther-Straub-Institute of Pharmacology and Toxicology, Ludwig-Maximilians University of Munich, Germany ) for the hLHR. This research was partially funded by United States-Israel Binational Science Foundation Grant 2005096 , by Niedersachsen-Israel research fund (Grant ZN2448 ). and by the Nutrigenomics and Functional Foods Research Center at The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem.

Keywords

  • FSH
  • G-protein-coupled receptor (GPCR)
  • Glycoprotein hormone receptor
  • LH
  • Molecular modeling
  • Signal transduction

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