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Stimulation of growth hormone by kisspeptin antagonists in ewes

Study · animal · The Journal of endocrinology · 2018 · DOI 10.1530/JOE-18-0074 · PMID 29549187

Plain-language summary

Paraphrased from the published abstract below — not a verdict on whether anything works.

In this study in ewes, researchers examined the effect of the kisspeptin antagonists p-234 and p-271 on growth hormone (GH) secretion, administered via lateral ventricle or third ventricle infusion in ovariectomized or anestrous ewes, and also tested central infusion of kisspeptin-10. The abstract reports clear and robust increases in GH secretion following infusion of kisspeptin antagonists p-234 and p-271, while central kisspeptin-10 infusion had no effect on GH secretion. Immunocytochemistry showed the kisspeptin receptor GPR54 was expressed by the majority of somatotropes in pituitary cells but was largely negative in other pituitary cell types. The authors state that blocking kisspeptin signaling stimulates GH secretion in ewes, likely by inhibiting endogenous kisspeptin activation of GPR54 on somatotropes.

Abstract

Kisspeptin signalling is indispensable for fertility, stimulating gonadotropin-releasing hormone (GnRH) secretion and mediating gonadal steroid feedback on GnRH neurons. Moreover, kisspeptin neurons have been implicated in other non-reproductive neuroendocrine roles. Kisspeptin appears to also regulate growth hormone secretion but much of the data appear contradictory. We sought to clarify a potential role of kisspeptin in growth hormone (GH) regulation by examining the effect of kisspeptin antagonists on GH secretion in ewes under various physiological conditions. Our data show clear and robust increases in GH secretion following lateral ventricle or third ventricle infusion of kisspeptin antagonists p-234 and p-271 in either ovariectomized or anestrous ewes. Central infusion of kisspeptin-10 had no effect on GH secretion. To determine the level at which kisspeptin may influence GH secretion, we examined expression of the cognate kisspeptin receptor, GPR54, in pituitary cells and showed by immunocytochemistry that the majority of somatotropes express GPR54 while expression was largely negative in other pituitary cells. Overall, we have demonstrated that blocking kisspeptin signalling by antagonists stimulates GH secretion in ewes and that this is likely mediated by inhibiting endogenous kisspeptin activation of GPR54 expressed on somatotropes. The findings suggest that endogenous kisspeptin inhibits GH secretion through GPR54 expressed on somatotropes.

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