Peer Review #2 of "Kisspeptin receptor agonist (FTM080) increased plasma concentrations of luteinizing hormone in anestrous ewes (v0.1)" [peer_review]

S Hileman
2015 unpublished
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)
more » ... r (VEH) intravenosuly. Blood was collected every 15 min before (1 hr) and after (1 hr) 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 hr) and after (4 hr) 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. Manuscript to be reviewed 22 These studies were designed to test and compare the effects of a KISS1R agonist (FTM080) and 23 kisspeptin on luteinizing hormone (LH) in vivo. 24 Methods: Experiment 1 (pilot study): Sheep were treated with FTM080 (500 pmol/kg 25 BW) or sterile water (VEH) intravenosuly. Blood was collected every 15 min before (1 hr) and 26 after (1 hr) treatment. Experiment 2: Sheep were treated with KP-10 (human Metastin 45-54; 27 500 pmol/kg BW), one of three dosages of FTM080 [500 (FTM080:500), 2500 (FTM080:2500), 28 or 5000 (FTM080:5000) pmol/kg BW], or VEH intravenously. Blood was collected every 15 29 min before (1 hr) and after (4 hr) treatment. 30 Results: Experiment 1: FTM080:500 increased (P < 0.05) plasma LH concentrations 31 when compared to VEH. The area under the curve (AUC) of LH following FTM080:500 32 treatment was also increased (P < 0.05). Experiment 2: Plasma LH concentrations increased (P < 33 0.05) following treatment with KP-10 and FTM080:5000 when compared to VEH and 34 FTM080:500. The AUC of LH following KP-10 was greater than (P < 0.05) all other treatments 35 and the AUC of LH following FTM080:5000 was greater than (P < 0.05) all treatments except 36 KP-10. 37 Conclusions: These data provide evidence to suggest that FTM080 stimulates the 38 gonadotropic axis of ruminants in vivo. Any increased half-life and comparable efficacy of 39 FTM080 to KP-10 in vitro does not appear to translate to in vivo in sheep. INTRODUCTION 41 Reproduction requires precise interactions among the brain, the pituitary, and the gonads 42 (gonadotropic-axis). Gonadotropin-releasing hormone (GnRH) from the hypothalamus has long 43 been considered a major regulator of the gonadotropic-axis because it controls the secretion of
doi:10.7287/peerj.1382v0.1/reviews/2 fatcat:455jfkggh5glpgo46lmv27doci