Organization of Two Independent Kisspeptin Systems Derived from Evolutionary-Ancient Kiss Genes in the Brain of Zebrafish

• Published in: Endocrinology (Philadelphia) 2011-04, Vol.152 (4), p.1527-1540
• Main Authors: Servili, Arianna, Le Page, Yann, Leprince, Jérôme, Caraty, Alain, Escobar, Sebastian, Parhar, Ishwar S, Seong, Jae Yong, Vaudry, Hubert, Kah, Olivier
• Format: Article
• Language: English
• Subjects: 17β-Estradiol; Animals; Antibodies; Apposition; Biochemistry, Molecular Biology; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Brain architecture; C-Terminus; Danio rerio; Estrogens; Estrogens - pharmacology; Evolution, Molecular; Fibers; Forebrain; Freshwater; Fundamental and applied biological sciences. Psychology; Gene regulation; Genes; Gonadotropin-Releasing Hormone - drug effects; Gonadotropin-Releasing Hormone - metabolism; Habenula - drug effects; Habenula - metabolism; Hybridization; Hypothalamus; Hypothalamus - drug effects; Hypothalamus - metabolism; Immunohistochemistry; In Situ Hybridization; Juveniles; Kiss1 protein; Kisspeptins; Life Sciences; Mesencephalon; Molecular biology; Neuroendocrine system; Neurons; Pituitary; Pituitary gland; Pituitary Gland - drug effects; Pituitary Gland - metabolism; Polymerase Chain Reaction; Preoptic area; Pyrrolidonecarboxylic Acid - analogs & derivatives; Pyrrolidonecarboxylic Acid - metabolism; Raphe nuclei; Raphe Nuclei - drug effects; Raphe Nuclei - metabolism; Receptors; Receptors, G-Protein-Coupled - metabolism; Receptors, Kisspeptin-1; Sex hormones; Thalamus; Tumor Suppressor Proteins - metabolism; Vertebrates; Vertebrates: endocrinology; Zebrafish; Zebrafish Proteins - metabolism
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2010-0948

The distributions of Kiss1- and Kiss2-expressing neurons, and their respective projections in relation with the distribution of Kiss receptors and GnRH neurons, are described in zebrafish. Kisspeptins are new actors in the neuroendocrine regulation of reproduction. In vertebrates, the number of kiss genes varies from none to three. Zebrafish have two kiss genes, kiss1 and kiss2, and two kiss receptors (GPR54), kiss1r and kiss2r. To provide detailed information on the organization of the kiss systems in zebrafish, antibodies were raised against the C terminus of zebrafish preproKiss1 and preproKiss2. Immunohistochemistry fully confirmed in situ hybridization data, showing that kiss1-expressing neurons are only located in the habenular nucleus, while kiss2-expressing neurons are found in the dorsal and ventral hypothalamus. Kiss1-expressing cells project only to the interpeduncular and raphe nuclei and strongly expressed the kiss1r receptor. In contrast, kiss2-expressing cells are mostly present in the dorsal and ventral hypothalamus and project widely into the subpallium, the preoptic area, the thalamus, the ventral and caudal hypothalamus, and the mesencephalon. All these regions strongly expressed the kiss2r messengers. Kiss2 fibers profusely innervate the ventral forebrain and notably made close apposition with GnRH3 neurons. Estrogen treatment of juvenile fish with estradiol causes increase in kiss2 and kiss2r expression. In the pituitary gland, no proKiss2- positive fibers were detected, while positive cells were observed in the pars intermedia. In addition to proposing a successful strategy to develop antibodies to kisspeptins, these data indicate that the kiss2 systems of zebrafish are implicated in reproductive events, while the kiss1 gene would play other functions that remain to be established.