title: Experimental and computational study of inter- and intra- species specificity of gonadotropins for various gonadotropin receptors.
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.
authors.affiliation: The Robert H. Smith Faculty of Agriculture, Food and Environment, Department of Animal Sciences, The Hebrew University of Jerusalem, Rehovot 76100, Israel.
authors.forename: Joseph
authors.initials: J
authors.lastname: Aizen
authors.forename: Noga
authors.initials: N
authors.lastname: Kowalsman
authors.forename: Makito
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Lian
authors.initials: L
authors.lastname: Hollander
authors.forename: Young Chang
authors.initials: YC
authors.lastname: Sohn
authors.forename: Goro
authors.initials: G
authors.lastname: Yoshizaki
authors.forename: Masha Y
authors.initials: MY
authors.lastname: Niv
authors.forename: Berta
authors.initials: B
authors.lastname: Levavi-Sivan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002417:Cattle; D002522:Chlorocebus aethiops; D004524:Eels / Q000235:genetics / Q000378:metabolism; D005640:Follicle Stimulating Hormone / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D007986:Luteinizing Hormone / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011962:Receptors, FSH / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011974:Receptors, LH / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012098:Reproduction / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013552:Swine / Q000235:genetics / Q000378:metabolism; D017210:Tilapia / Q000235:genetics / Q000378:metabolism; D014337:Trout / Q000235:genetics / Q000378:metabolism
chemical_list: D011962:Receptors, FSH; D011974:Receptors, LH; D011994:Recombinant Proteins; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone