Kisspeptin Receptor Agonists Stimulates Luteinizing hormone in Sheep 1 TITLE KISSPEPTIN RECEPTOR AGONIST ( FTM 080 ) INCREASED PLASMA CONCENTRATIONS OF LUTEINIZING HORMONE IN ANESTROUS EWES

Background/Aims: 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. PeerJ PrePrints | https://dx.doi.org/10.7287/peerj.preprints.912v1 | CC-BY 4.0 Open Access | rec: 19 Mar 2015, publ: 19 Mar 2015 P re P ri n ts Kisspeptin Receptor Agonists Stimulates Luteinizing hormone in Sheep 2 These studies were designed to test and compare the effects of a KISS1R agonist (FTM080) and kisspeptin on luteinizing hormone (LH) in vivo. Methods: 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 hr) and after (1 hr) treatment. 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 hr) and after (4 hr) treatment. Results: 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). 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