Central ghrelin production does not substantially contribute to systemic ghrelin concentrations: a study in two subjects with active acromegaly

Abstract

Introduction: In an animal model of acromegaly (PEPCK-hGH transgenic mice), low systemic levels of ghrelin have been observed compared with normal mice. We hypothesized that systemic circulating ghrelin levels are also decreased in humans with active acromegaly and that the contribution of central ghrelin production to systemic ghrelin levels is minimal. Objectives: The aim of the present study was to investigate, in two subjects with active acromegaly, whether there are differences between systemic ghrelin levels and ghrelin concentrations in the petrosal sinus. Design: We measured systemic and central ghrelin levels in these two acromegalic patients by bilateral simultaneous inferior petrosal sinus sampling. Central and systemic blood samples were drawn before and 1, 5, 10, 15 and 20 min after stimulation with GH-releasing hormone (GHRH). Ghrelin was measured with a commercially available radioimmunoassay. Results: In one acromegalic subject, the baseline systemic and central ghrelin levels were within the same range as in two non-acromegalic obese subjects. No gradient could be observed between central and systemic ghrelin concentrations. Stimulation with GHRH did not change the ghrelin concentrations in this patient. In the other acromegalic subject, the systemic ghrelin levels were also in the same range as in two non-acromegalic obese subjects. However, in this subject, baseline ghrelin concentrations in the right inferior petrosal vein were considerably lower than the systemic ghrelin concentrations, indicating a peripheral over central gradient. Administration of GHRH induced a significant rise in central ghrelin concentrations in the right inferior petrosal vein. Ghrelin levels in the left inferior petrosal vein and systemic ghrelin levels were in the normal range and GHRH stimulation did not change these concentrations. Conclusions: The absence of a central over peripheral ghrelin gradient in these two acromegalics indicated that circulating ghrelin is mainly produced peripherally. Circulating systemic ghrelin levels were not decreased in these two subjects with active acromegaly.

Sleep enhances nocturnal plasma ghrelin levels in healthy subjects

“…Small quantities might also be produced in the hypothalamus (for review see Ref. 9), but these are very unlikely to contribute to systemic levels (34). Hence, it is almost certain that the increased ghrelin levels that we found in sleeping subjects are due to peripheral production.…”

Altered fasting and postprandial plasma ghrelin levels in patients with liver failure are normalized after liver transplantation

“…Although the relationship between ghrelin and GH secretion is controversial. In acromegaly, a pathophysiological model of increased GH secretion, some studies have found normal ghrelin levels (37)(38)(39)(40), while others have found decreased ghrelin levels in patients with acromegaly (41)(42)(43), suggesting that increased GH could contribute toward the decreased ghrelin levels, in a classic feedback manner. In liver failure patients, we found decreased IGF1 and increased GH.…”

Fasting and postprandial plasma ghrelin levels are decreased in patients with liver failure previous to liver transplantation

“…Ghrelin is a potent stimulus for GH secretion [13,29] and, at least under certain physiologic conditions, ghrelin modulates the regulation of GH secretion [57], although the relationship between ghrelin and GH secretion is controversial. In acromegaly, a pathophysiological model of increased GH secretion, some studies have found normal ghrelin levels [58][59][60][61], while others have found decreased ghrelin levels in patients with acromegaly [62][63][64], suggesting that increased GH could contribute towards the decreased ghrelin levels in a classic feedback manner. This said, the number of patients used in the correlation studies was small, and the results should be taken with caution.…”

“…As a control group 10 age and BMI matched healthy or overweight subjects (6 male, 4 female), selected from a pool of volunteers available to our unit, were included, median (range) age of 58.5 (54)(55)(56)(57)(58)(59)(60)(61)(62)(63)(64)(65) years, median (range) BMI of 25.4 (20-29.7) kg/m 2 .…”