In rats, giving ghrelin (the hormone that GHRP‑6 mimics) either directly into the brain or into the bloodstream raises the amount of oxytocin in the blood. Blocking ghrelin with the antagonist [d‑Lys³]‑GHRP‑6 cuts this oxytocin boost. This shows that the ghrelin system can directly trigger oxytocin release.

The hypothalamic⁻pituitary axis by secreting neuropeptides plays a key role in metabolic homeostasis. In light of the metabolic regulation, oxytocin is a potential neuropeptide for therapies against obesity and related disorders. The aim of our study is to measure ghrelin-induced oxytocin secretion in rats and to detect the changes after administration of ghrelin antagonist. Ghrelin was administrated centrally (intracerebroventricular, i.c.v., 1.0, 10.0, and 100.0 pmol) or systemically (intravenous, i.v., 1.0, and 10.0 nmol). [d-Lys³]-GHRP-6 ghrelin antagonist was injected 15 min before ghrelin injection in a dose of 10.0 pmol i.c.v. and 10.0 nmol i.v. Either i.c.v. or i.v. administration of ghrelin dose-dependently increased the plasma oxytocin concentration. Following pretreatment with the ghrelin antagonist [d-Lys³]-GHRP-6, the high plasma oxytocin level induced by ghrelin was significantly reduced. The results indicate that the release of oxytocin is influenced directly by the ghrelin system. Examination of the mechanism of ghrelin-induced oxytocin secretion is a new horizon for potential therapeutic options.