title: Identification of a novel kisspeptin with high gonadotrophin stimulatory activity in the dog.
abstract: Kisspeptin (KISS1) and its receptor (KISS1r) are essential for normal reproductive function in many species, but the role of kiss1/kiss1r signalling in the dog has not yet been elucidated. The aims of this study were to identify the canine kiss1 and kiss1r genes and to determine gonadotrophin and oestradiol stimulatory activity of KP-10, the shortest biologically active form of KISS1. Canine kiss1 and kiss1r genes were localized by comparing the reference dog genome with relevant human cDNA sequences, using BLASTn software. The amino acid sequence of canine KP-10 (YNWN V FGLR Y ) differs at two positions from human KP-10 (YNWN S FGLR F ). A single bolus of canine KP-10 was administered intravenously to anoestrous Beagle bitches in dosages of 0, 0.1, 0.2, 0.3, 0.5, 1, 5, 10, and 30 μg/kg. Blood samples were collected before and after canine KP-10 administration for the measurement of plasma luteinizing hormone (LH, all doses), follicle-stimulating hormone (FSH) and oestradiol (1-30 μg/kg). From 0.2 μg/kg onwards, canine KP-10 resulted in a rapid and robust rise in plasma LH concentration (max. at 10 min). KP-10 also resulted in a rapid and robust rise in plasma FSH concentration (max. at 10-20 min). Plasma oestradiol concentration increased significantly after dosages of 1, 5, and 10 μg/kg and reached a maximum at 60-90 min. In conclusion, canine KP-10 is a potent kisspeptin which elicits robust gonadotrophin and oestradiol responses in anoestrous bitches, suggesting that canine kiss1/kiss1r are cogent targets for modulating reproduction in dogs.
authors.affiliation: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
authors.forename: Karin H J
authors.initials: KH
authors.lastname: Albers-Wolthers
authors.forename: Jeffrey
authors.initials: J
authors.lastname: de Gier
authors.forename: Hans S
authors.initials: HS
authors.lastname: Kooistra
authors.forename: Victor P M G
authors.initials: VP
authors.lastname: Rutten
authors.forename: Peter J S
authors.initials: PJ
authors.lastname: van Kooten
authors.forename: Janneke J
authors.initials: JJ
authors.lastname: de Graaf
authors.forename: Peter A J
authors.initials: PA
authors.lastname: Leegwater
authors.forename: Robert P
authors.initials: RP
authors.lastname: Millar
authors.forename: Auke C
authors.initials: AC
authors.lastname: Schaefers-Okkens
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D019540:Area Under Curve; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000097:blood; D005640:Follicle Stimulating Hormone / Q000097:blood*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D007987:Gonadotropin-Releasing Hormone / Q000097:blood*; D006801:Humans; D059648:Kisspeptins / Q000235:genetics* / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000097:blood*; D012333:RNA, Messenger / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D000074502:Receptors, Kisspeptin-1
chemical_list: C106628:KISS1 protein, human; C118688:KISS1R protein, human; D059648:Kisspeptins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone