GH response to ghrelin in subjects with congenital GH deficiency: evidence that ghrelin action requires hypothalamic–pituitary connections

Abstract

Objectives: Evaluation of GH response to ghrelin in patients with GH deficiency (GHD) may help to elucidate the site and mechanism of action of ghrelin. We aimed to investigate the GH-releasing effect of ghrelin in children and young adults with childhood-onset GHD. Design: All subjects underwent ghrelin testing and neuro-imaging examination. Magnetic resonance imaging evidenced the presence of a vascular pituitary stalk (VPS) or its complete absence (PSA). Patients and methods: Seventeen prepubertal children and nine adult patients with childhood-onset GHD were selected for the study. The children were enrolled at a median age of 5.8 years. The adult subjects were included at a median age of 23.3 years. The diagnosis of GHD in the adult patients had been established at a median age of 8.5 years. Ghrelin was administered at a dose of 1 mg/kg body weight, i.v. at time zero, and blood for GH determination was obtained at 0, 15, 30, 45, 60, 75, 90, 105 and 120 min.

Acylated ghrelin as a provocative test for the diagnosis of GH deficiency in adults

“…Previous studies have clearly demonstrated that ghrelin is a potent natural GH secretagogue (16,18,19,20,21,25), and that its acute administration induces a strong GH release, similar to that recorded after stimulation with GHRH in combination with ARG, and higher than that provoked by insulin-induced hypoglycemia (25). The present study confirms that ghrelin's effect is equal to GHRHCARG and stronger than ITT both in non-GHD and GHD.…”

“…The present study confirms that ghrelin's effect is equal to GHRHCARG and stronger than ITT both in non-GHD and GHD. The strong GH-releasing effect of ghrelin, as well as of several synthetic GHS, has been explained by the dual action exerted mostly at the hypothalamic level, but also on the pituitary (19,20,21). Indeed, ghrelin seems to be able to trigger hypothalamic GHRH activity, and activate GHS receptor in the pituitary, counteracting somatostatin's inhibitory action (28).…”

“…Ghrelin exerts a strong and dosedependent GH-releasing effect (19) that potentially includes activity at the pituitary and/or hypothalamus. The effect of ghrelin in vivo is stronger than in vitro (19), and it is dependent on the presence of GHRH (18,19,20,21). Moreover, ghrelin shows an additive or even synergistic effect on GHRH-stimulated GH release (18) and prevents cyclic refractoriness to GHRH (19).…”

“…Moreover, ghrelin shows an additive or even synergistic effect on GHRH-stimulated GH release (18) and prevents cyclic refractoriness to GHRH (19). In addition, ghrelin-mediated GH secretion is reduced, although not completely abolished, in animals and patients with lesions of the pituitary stalk, suggesting that the main action of ghrelin occurs at the hypothalamic level (20,21).…”

Ghrelin and growth hormone serum levels during the clonidine test in children with short stature and variable growth hormone status

“…According to Maghnie et al, 27 children and adults with GHD demonstrate a rise in GH levels following an increase in the circulating ghrelin. The same investigators, using brain MRI, also demonstrated that GH response to ghrelin requires the functional influence of puberty, which has been found to affect ghrelin levels.…”