Kisspeptin stimulates growth hormone release by utilizing neuropeptide y pathways and is dependent on the presence of ghrelin in the ewe

Chad D. Foradori, Brian K. Whitlock, Jay A. Daniel, Arthur D. Zimmerman, Melaney A. Jones, Casey C. Read, Barbara P. Steele, Jeremy T. Smith, Iain J. Clarke, Theodore H. Elsasser, Duane H. Keisler, James L. Sartin

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)


Although kisspeptin is the primary stimulator of gonadotropin-releasing hormone secretion and therefore the hypothalamic-pituitary-gonadal axis, recent findings suggest kisspeptin can also regulate additional neuroendocrine processes including release of growth hormone (GH). Here we show that central delivery of kisspeptin causes a robust rise in plasmaGHin fasted but not fed sheep.Kisspeptin-inducedGHsecretion was similar inanimals fasted for 24 hours andthose fastedfor 72 hours, suggestingthat the factors involved in kisspeptin-induced GH secretion are responsive to loss of food availability and not the result of severe negative energy balance. Pretreatment with the neuropeptide Y (NPY) Y1 receptor antagonist, BIBO 3304, blocked the effects of kisspeptin-induced GH release, implicating NPY as an intermediary. Kisspeptin treatment induced c-Fos in NPY and GH-releasing hormone (GHRH) cells of the arcuate nucleus. The same kisspeptin treatment resulted in a reduction in c-Fos in somatostatin (SS) cells in the periventricular nucleus. Finally, blockade of systemic ghrelin release or antagonism of the ghrelin receptor eliminated or reduced the ability of kisspeptin to induce GH release, suggesting the presence of ghrelin is required for kisspeptin-induced GH release in fasted animals. Our findings support the hypothesis that during shortterm fasting, systemic ghrelin concentrations andNPY expression in the arcuate nucleus rise. This permits kisspeptin activation of NPY cells. In turn, NPY stimulates GHRH cells and inhibits SS cells, resulting in GH release. We propose a mechanism by which kisspeptin conveys reproductive and hormone status onto the somatotropic axis, resultinginalterations inGHrelease.

Original languageEnglish
Pages (from-to)3526-3539
Number of pages14
Issue number10
Publication statusPublished - 1 Oct 2017


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