Progress 03/15/10 to 06/30/12
Outputs
OUTPUTS: Experiments were conducted at Auburn, University of Tennessee and Monash University (Australia). Samples have been analyzed for multiple hormones and immunohistochemistry and statistics completed. Seminars have been given on this work at 6 Universities in 4 countries and 4 Universities in the US in 2011-2012. PARTICIPANTS: Sartin, J. L. Auburn University, Auburn, AL ; Clarke, I. J. Monash University, Melbourne, Australia; Daniel, J. A. Berry College, Rome, GA; Millar, R. MRC, Edinburgh, Scotland; Whitlock, B. K.University of Tennessee, Knoxville, TN ; Wilborn, R. R. Auburn University, Auburn, AL; Chad Foradori, Auburn University and Theodore Elsasser, USDA, Beltsville, MD all worked on the project either at Auburn or at their home institutions. In addition, Barabra Steele served as a research technician at Auburn and David Daniel as an animal technician. Kate Kirby, a veterinary student learning about research, worked as research assistant on this project. TARGET AUDIENCES: Science based educational audiences are the target audience through meetings and class room instruction. PROJECT MODIFICATIONS: The proposed mechanism of action for kisspeptin was to involve GH releasing hormone and somatostatin. Somatostatin immunohistochemistry revealed a decrease in somatostatin neuron activation which is indicative of a role for these neurons, but direct mesaurement of circulating somatastatin into the portal vein indicated this was not due to endocrine effects, but possibly another pathway. Based on this result, we examined an alternate hypothesis that neuropeptide Y (NPY) activated the vagus nerve to release Ghrelin which would activate GH release. Infusion of a muscarinic cholinergic antagonist or a Ghrelin receptor antagonist provided mixed results.
Impacts
The kisspeptin molecule activates Growth hormone (GH) release through hypothalamic mechanisms. Fasting upregulates the release of GH by kisspeptin whereas feeding diminishes kisspeptin actions on GH. Examining the neuropeptide Y (NPY) pathway indicated that an antagonist to the NPY-Y1 receptor blocks the effect, suggesting the NPY pathway is a mediator of kisspeptin actions to release GH. Immunohistochemistry defines a role for somatostatin nerons in the process as well. However, portal vein samples indicated no change in GH releasing hormone or somatostatin. Another mechanism was then investigated whereby NPY activates the vagus nerve to release Ghrelin which in turn, releases GH. We were able to show that blocking the acetylcholine receptor prevented the effects of kisspeptin, thus suggesting acetylcholine outside the hypothalamus was involved in the mechanism and is consistent with the new hypothesis. Attempts to block Ghrelin receptor function did not yield conclusive results but this pathway remains the most likely to explain the results obtained.
Publications
- Whitlock BK, JA Daniel RR Wilborn, BP Steele, JL Sartin. Effect of stage of estrous cycle on kisspeptin-stimulated luteinizing hormone and growth hormone concentrations in heifers. ASAS-AAPA Joint Annual Meeting, Mara del Plata, Argentina. October, 2011.
- Whitlock BK, JA Daniel, RR Wilborn, HS Maxwell, BP Steele, JL Sartin. Effects of kisspeptin to regulate growth hormone and luteinizing hormone in lactating dairy cows. Journal of Animal Science and Biotechnology 2:131-140, 2011.
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Progress 03/15/10 to 03/14/11
Outputs
OUTPUTS: Activities. Experiments have been conducted on Objective 1, experiment 1 for the effects of fasting on kisspeptin stimulated growth hormone release in sheep. Samples have been analyzed and statistical analysis is underway. Collection of samples from sheep stimulated with estradiol and kisspeptin (experiment 2) are underway as is the immunohistochemistry component for objective 2, experiment 1. The remainder of objective 2 will be initiated with the coinvestigators in year two along with remaining experiments in Objective 3. PARTICIPANTS: Sartin, J. L. Auburn University, Auburn, AL ; Clarke, I. J. Monash University, Melbourne, Australia; Daniel, J. A. Berry College, Rome, GA; Millar, R. MRC, Edinburgh, Scotland; Whitlock, B. K.University of Tennessee, Knoxville, TN ; Wilborn, R. R. Auburn University, Auburn, AL all worked on the project either at Auburn or at their home institutions. In addition, Barabra Steele served as a research technician at Auburn and David Daniel as an animal technician. Kate Kirby and Ashley Ladegast are veterinary students learning about research and worked as research assistants on this project. TARGET AUDIENCES: Science based educational audiences are the target audience through meetings and class room instruction. PROJECT MODIFICATIONS: Not relevant to this project.
Impacts
There is clear evidence that kisspeptin is not only a regulator of the reproductive system and is responsive to nutritional inputs tot he brain, but that kisspeptin can regulate growth hormone secretion. Evidence suggests that fasting upregulates the effects of kisspeptin and the effects are mediated via neuropeptide Y dependent mechanisms.
Publications
- Whitlock, BK, Daniel JA, Sartin JL. (2010) Changes in plasma concentrations of growth hormone and luteinizing hormone in ewes following central and peripheral treatment with kisspeptin. American Society of Animal Science. 88 (suppl 2):112.
- Whitlock BK, Daniel JA, Wilborn RR, Maxwell HS, Steele BP, Sartin JL. (2010) Interaction of kisspeptin and the somatotropic axis. Neuroendocrinology 92:178-188.
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