Kisspeptin receptor agonist (FTM080) increased plasma concentrations of luteinizing hormone in anestrous ewes
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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 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.
Cite this as
2015. Kisspeptin receptor agonist (FTM080) increased plasma concentrations of luteinizing hormone in anestrous ewes. PeerJ PrePrints 3:e912v1 https://doi.org/10.7287/peerj.preprints.912v1note This preprint is not peer-reviewed. You may wish to reference the subsequent peer-reviewed version of this article.
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This is a submission to PeerJ for review.
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Competing Interests
The authors have no competing interests to report.
Author Contributions
Brian K Whitlock conceived and designed the experiments, performed the experiments, analyzed the data, wrote the paper, prepared figures and/or tables, reviewed drafts of the paper.
Joseph A Daniel performed the experiments, analyzed the data, reviewed drafts of the paper.
Lisa L Amelse reviewed drafts of the paper.
Valeria M Tanco wrote the paper, reviewed drafts of the paper.
Kelly A Chameroy performed the experiments, wrote the paper, reviewed drafts of the paper.
F Neal Schrick contributed reagents/materials/analysis tools.
Animal Ethics
The following information was supplied relating to ethical approvals (i.e., approving body and any reference numbers):
1) Berry College Institutional Animal Care and Use Committee. 2) 2011/12-010
Funding
This project was supported by the Center of Excellence in Livestock Diseases and Human Health from the University of Tennessee, College of Veterinary Medicine. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
