Ghrelin Main Action on the Regulation of Growth Hormone Release Is Exerted at Hypothalamic Level

Abstract

Ghrelin, a recently isolated hormone, seems to participate in the physiological regulation of GH secretion. Exogenously administered ghrelin stimulates GH discharge in all species so far tested including man, but whether this action is exerted at pituitary or alternatively at hypothalamic level is not known at present. To understand the point of ghrelin action a group of patients with organic lesion mainly in the hypothalamic area and matched controls were studied. Patients showed a severe GH deficiency after hypothalamic stimulation (ITT), but partial response after GHRH administration. Cases and controls were tested on three separate days by either ghrelin; GHRH; and ghrelin plus GHRH; always at 1 micro g/Kg iv. The mean GH peak after stimulation in the patients were: 0.4 +/- 0.1 micro g/L by ITT; 3.1 +/- 0.5 micro g/L after GHRH; 2.0 +/- 0.8 micro g/L after ghrelin; and 9.6 +/- 2.9 micro g/L after the combination of GHRH plus ghrelin. In the controls GHRH induced a GH peak of 21.2 +/- 7.5 micro g/L, and 75.1 +/- 16.0 micro g/L after ghrelin with a peak after GHRH + ghrelin of 103.5 +/- 26.4 micro g/L. These data indicate that when hypothalamic structures are not operative ghrelin, either alone or in combination with GHRH, is not able to significantly release GH. In addition to postulating a hypothalamic point of action for the ghrelin-induced GH secretion, these results suggests that ghrelin will not have significant clinical utility in patients with GH deficiency due to organic lesion.

Ghrelin test for the assessment of GH status in successfully treated patients with acromegaly

“…We and others have shown that GHS retain their GH-releasing effect in active acromegaly (19). Ghrelin, the natural ligand of the GHS-R with more potent GH-releasing activity and specificity was found to elicit an increase in GH in newly diagnosed acromegalic patients, and the response was positively correlated with basal IGF-I concentrations (20,21).…”

“…bolus). This dose of ghrelin has previously been shown to be effective in stimulating GH release in humans (20). Samples for GH were taken at 0, 15, 30 and 45 min after ghrelin administration.…”

“…Ghrelin, the natural ligand of the GHS-R, has potent GH-releasing activity and specificity. It was found to increase GH release in newly diagnosed acromegalic patients, a response that is positively correlated with basal IGF-I concentrations (20,21). Aimaretti et al have administered ghrelin to patients with isolated severe GH deficiency and have clearly shown that the GH response to ghrelin is severely impaired (22).…”

Ghrelin, an endogenous growth hormone secretagogue with diverse endocrine and nonendocrine effects

“…The GH response to ghrelin is partially inhibited by GHRH receptor antagonists and disruption of communication between the hypothalamus and pituitary gland, 75,76 supporting the assumption that the effect of ghrelin on GH secretion is primarily mediated by GHRH-secreting neurons at the level of thehypothalamus. 21,74,76,77 In anesthetized rats, ghrelin administered IV stimulates GH release without affecting secretion of other adenohypophyseal hormones.…”

“…21,74,76,77 In anesthetized rats, ghrelin administered IV stimulates GH release without affecting secretion of other adenohypophyseal hormones. 8 Also, in cultured rat pituitary cells, ghrelin stimulates GH release in a dosedependent manner without affecting the release of other pituitary hormones, even at high concentrations.…”