title: Functional and evolutionary analysis of flatfish gonadotropin receptors reveals cladal- and lineage-level divergence of the teleost glycoprotein receptor family.
abstract: Pituitary gonadotropins, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) act via their cognate glycoprotein hormone receptors (GpHRs), FSH receptor (FSHR), and LH/choriogonadotropin receptor (LHCGR) to regulate gonad physiology. Here, we show that the flatfish Senegalese sole (Solea senegalensis) expresses functional isoforms of fshr and lhcgr, but the genomic origin, ligand activation, and tissue distribution of the receptor transcripts are more complex than expected. By integrating the molecular phylogeny of GpHRs with the syntenic loci of vertebrate orthologs, and by subsequently characterizing the physical maps with the phylogeny of flanking genes, we found that vertebrate GpHRs have undergone a divergent evolution. In Teleostei, fshr genes have a common descent and can be classified as fshra, whereas lhcgrb genes exist as alternatively coded genes even in closely related species. Structural analyses of the receptors revealed that Fshra has an elongated ligand-binding domain, containing an extra leucine-rich repeat that specifically arose in the Acanthomorpha because of exon duplication. Ectopic expression in Xenopus laevis oocytes demonstrated that sole Fshra responded to piscine Fsh and Lh, whereas Lhcgrba was preferentially activated by its cognate hormone. The expression pattern of sole fshra and lhcgrba in gonads during the reproductive cycle was consistent with earlier observations wherein Fshra regulates ovarian growth and spermatogenesis and Lhcgrb triggers gamete maturation, respectively. However, contrary to observations in other teleosts, fshra was localized exclusively in Sertoli cells of the testis, whereas lhcgrba was expressed in Leydig cells as well as in spermatids. These results demonstrate the presence of alternatively coded lhcgr isoforms (lhcgrba and lhcgrbb) in teleosts and suggest a role of the lhcgrba receptor in the differentiation of spermatids into spermatozoa in Senegalese sole.
authors.affiliation: Laboratory of Institut de Recerca i Tecnologia Agroalimentàries-Institut de Ciències del Mar, Consejo Superior de Investigaciones Científicas, Barcelona, Spain.
authors.forename: François
authors.initials: F
authors.lastname: Chauvigné
authors.forename: Angèle
authors.initials: A
authors.lastname: Tingaud-Sequeira
authors.forename: María J
authors.initials: MJ
authors.lastname: Agulleiro
authors.forename: Magdalena
authors.initials: M
authors.lastname: Calusinska
authors.forename: Ana
authors.initials: A
authors.lastname: Gómez
authors.forename: Roderick Nigel
authors.initials: RN
authors.lastname: Finn
authors.forename: Joan
authors.initials: J
authors.lastname: Cerdà
mesh_terms: D000818:Animals; D019143:Evolution, Molecular; D005091:Exons; D005260:Female; D005412:Flatfishes / Q000235:genetics / Q000254:growth & development*; D005640:Follicle Stimulating Hormone / Q000378:metabolism / Q000494:pharmacology; D020440:Gene Duplication; D005854:Germ Cells / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D000090263:Leucine-Rich Repeat Proteins; D007985:Leydig Cells / Q000166:cytology / Q000378:metabolism; D007986:Luteinizing Hormone / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D010053:Ovary / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D010802:Phylogeny; D011506:Proteins / Q000235:genetics; D011962:Receptors, FSH / Q000235:genetics* / Q000378:metabolism; D011974:Receptors, LH / Q000235:genetics* / Q000378:metabolism; D012708:Sertoli Cells / Q000166:cytology / Q000378:metabolism; D013087:Spermatids / Q000166:cytology / Q000378:metabolism; D013091:Spermatogenesis / Q000187:drug effects / Q000235:genetics
chemical_list: D000090263:Leucine-Rich Repeat Proteins; D011506:Proteins; D011962:Receptors, FSH; D011974:Receptors, LH; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone