title: Kisspeptin receptor agonist (FTM080) increased plasma concentrations of luteinizing hormone in anestrous ewes.
abstract: Kisspeptin receptor (KISS1R) agonists with increased half-life and similar efficacy to kisspeptin in vitro may provide beneficial applications in breeding management of many species. However, many of these agonists have not been tested in vivo. These studies were designed to test and compare the effects of a KISS1R agonist (FTM080) and kisspeptin on luteinizing hormone (LH) in vivo. In experiment 1 (pilot study), sheep were treated with FTM080 (500 pmol/kg BW) or sterile water (VEH) intravenosuly. Blood was collected every 15 min before (1 h) and after (1 h) treatment. In experiment 2, sheep were treated with KP-10 (human Metastin 45-54; 500 pmol/kg BW), one of three dosages of FTM080 (500 (FTM080:500), 2500 (FTM080:2500), or 5000 (FTM080:5000) pmol/kg BW), or VEH intravenously. Blood was collected every 15 min before (1 h) and after (4 h) treatment. In experiment 1, FTM080:500 increased (P < 0.05) plasma LH concentrations when compared to VEH. The area under the curve (AUC) of LH following FTM080:500 treatment was also increased (P < 0.05). In experiment 2, plasma LH concentrations increased (P < 0.05) following treatment with KP-10 and FTM080:5000 when compared to VEH and FTM080:500. The AUC of LH following KP-10 was greater than (P < 0.05) all other treatments and the AUC of LH following FTM080:5000 was greater than (P < 0.05) all treatments except KP-10. These data provide evidence to suggest that FTM080 stimulates the gonadotropic axis of ruminants in vivo. Any increased half-life and comparable efficacy of FTM080 to KP-10 in vitro does not appear to translate to in vivo in sheep.
authors.affiliation: Department of Large Animal Clinical Sciences, The University of Tennessee , Knoxville, TN , United States.
authors.forename: Brian K
authors.initials: BK
authors.lastname: Whitlock
authors.affiliation: Department of Animal Science, Berry College , Mt. Berry, GA , United States.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Daniel
authors.affiliation: Department of Large Animal Clinical Sciences, The University of Tennessee , Knoxville, TN , United States.
authors.forename: Lisa L
authors.initials: LL
authors.lastname: Amelse
authors.affiliation: Department of Small Animal Clinical Sciences, The University of Tennessee , Knoxville, TN , United States.
authors.forename: Valeria M
authors.initials: VM
authors.lastname: Tanco
authors.affiliation: Department of Large Animal Clinical Sciences, The University of Tennessee , Knoxville, TN , United States.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Chameroy
authors.affiliation: Department of Animal Science, The University of Tennessee , Knoxville, TN , United States.
authors.forename: F Neal
authors.initials: FN
authors.lastname: Schrick
keywords: Agonist; Kisspeptin; Luteinizing hormone; Sheep