title: Kisspeptin Antagonists Reveal Kisspeptin 1 and Kisspeptin 2 Differential Regulation of Reproduction in the Teleost, Morone saxatilis.
abstract: The importance of kisspeptin in regulating vertebrate reproduction has been well established, but the exact mechanism continues to unfold. Unlike mammals, many lower vertebrates possess a dual kisspeptin system, Kiss1 and Kiss2. To decipher the roles of the kisspeptins in fish, we identified two potential kisspeptin antagonists, pep 234 and pep 359, by screening analogs for their ability to inactivate striped bass Kiss1 and Kiss2 receptors expressed in COS7 cells. Pep 234 (a mammalian KISS1 antagonist) antagonizes Kiss1r signaling activated by Kiss1 and Kiss2, and pep 359 (a novel analog) antagonizes Kiss2 activation of both receptors. In vitro studies using brain slices demonstrated that only Kiss2 can upregulate the expression of the hypophysiotropic gnrh1, which was subsequently diminished by pep 234 and pep 359. In primary pituitary cell cultures, the two antagonists revealed a complex network of putative endogenous and exogenous regulation by kisspeptin. While both kisspeptins stimulate Fsh expression and secretion, Kiss2 predominately induces Lh secretion. Pep 234 and 359 treatment of spawning males hindered sperm production. This effect was accompanied with decreased brain gnrh1 and gnrh2 mRNA levels and peptide content in the pituitary, and increased levels of pituitary Lh, probably due to attenuation of Lh release. Strikingly, the mRNA levels of arginine-vasotocin, the neurons of which in the preoptic area coexpress kiss2r, were dramatically reduced by the antagonists. Our results demonstrate differential actions of Kiss1 and Kiss2 systems along the hypothalamic-pituitary axis and interactions with other neuropeptides, and further reinforce the importance of kisspeptin in the execution of spawning.
authors.affiliation: Insitute of Marine and Environmental Technology, Department of Marine Biotechnology, University of Maryland Baltimore County, Baltimore, Maryland.
authors.forename: Nilli
authors.initials: N
authors.lastname: Zmora
authors.affiliation: Insitute of Marine and Environmental Technology, Department of Marine Biotechnology, University of Maryland Baltimore County, Baltimore, Maryland.
authors.forename: John David
authors.initials: JD
authors.lastname: Stubblefield
authors.affiliation: Insitute of Marine and Environmental Technology, Department of Marine Biotechnology, University of Maryland Baltimore County, Baltimore, Maryland.
authors.forename: Ten-Tsao
authors.initials: TT
authors.lastname: Wong
authors.affiliation: Department of Animal Sciences, Faculty of Agriculture, Food and Environment, the Hebrew University, Rehobot, Israel.
authors.forename: Berta
authors.initials: B
authors.lastname: Levavi-Sivan
authors.affiliation: Mammal Research Institute, Department of Zoology, University of Pretoria, Pretoria, South Africa University of Cape Town/Medical Research Council Receptor Biology Unit, Institute for Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: Robert Peter
authors.initials: RP
authors.lastname: Millar
authors.affiliation: Insitute of Marine and Environmental Technology, Department of Marine Biotechnology, University of Maryland Baltimore County, Baltimore, Maryland zohar@umbc.edu.
authors.forename: Yonathan
authors.initials: Y
authors.lastname: Zohar
mesh_terms: D000818:Animals; D001492:Bass / Q000235:genetics*; D001923:Brain Chemistry / Q000235:genetics; D019556:COS Cells; D002522:Chlorocebus aethiops; D007987:Gonadotropin-Releasing Hormone / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D059648:Kisspeptins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000378:metabolism; D010902:Pituitary Gland / Q000378:metabolism; D061251:Primary Cell Culture; D012333:RNA, Messenger / Q000096:biosynthesis; D012098:Reproduction / Q000235:genetics*; D014668:Vasotocin / Q000378:metabolism
chemical_list: D059648:Kisspeptins; D012333:RNA, Messenger; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D014668:Vasotocin
keywords: gonadotropes; neuroanatomy; neuropeptides; reproductive axis; spawning