Ghrelin administration affects circulating pituitary and gastro-entero-pancreatic hormones in acromegaly

Abstract

Objective: Ghrelin, a gut -brain peptide involved in the control of energy homeostasis, affects anteropituitary and gastro-entero-pancreatic (GEP) hormone secretion in healthy subjects. We aimed to verify whether such hormonal responses are retained in acromegaly, a disease characterized by high GH, subnormal ghrelin and abnormal GEP hormone levels. Design and methods: The effect of ghrelin (3.3 mg/kg given after overnight fasting as an i.v. bolus) on GH, prolactin (PRL), adrenocorticotropin (ACTH), cortisol, insulin, glucose, total somatostatin (SS) and pancreatic polypeptide (PP) circulating levels were evaluated in seven non-diabetic patients with newly diagnosed acromegaly and in nine healthy controls. Results: Ghrelin elicited a prompt, marked increase of serum GH and PRL levels in all normal (from 1.6^0.6 to 52.9^7.8 and from 9.7^0.8 to 24.2^4.8 mg/l (means^S.E.M.), respectively) and acromegalic subjects (from 11.2^4.9 to 91.6^21.0 and from 42.9^26.1 to 113.8^79.0 mg/l, respectively). Both plasma ACTH and serum cortisol levels rose significantly in the controls, whereas the cortisol response was blunted in the acromegalic patients. Glucose levels rose earlier and insulin levels fell later in all subjects, with a significantly greater net insulin decrease in acromegalic than in healthy subjects (2 80^21 vs 2 17^4 pmol/l, P , 0.01). A prompt PP rise and a biphasic SS response occurred in all controls, whereas in the acromegalic group the PP response (from 26.1^5.0 to 92.2^39.0 pmol/l) and the SS response (from 11.9^3.0 to 19.7^4.0 ng/l) were quite variable. Conclusions: Ghrelin affects both pituitary and GEP hormones in acromegalic patients as in normal subjects. These findings suggest that ghrelin actions on the energy balance are mediated by complex interactive endocrine loops that involve also the gut and pancreas.

Novel ghrelin analogs with improved affinity for the GH secretagogue receptor stimulate GH and prolactin release from human pituitary cells

“…The stimulatory effect of ghrelin on PRL secretion in vivo in humans is slight (24,25), in accordance with the previous studies of GHRPs in humans (43).…”

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).…”

“…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).…”

Akromegalia może wiązać się z zaburzeniami rozkurczu dolnego zwieracza przełyku (LES)

“…Ghrelin enhances upper gastrointestinal motility and gastric emptying through the vagus nerves [27][28][29]. It has been shown that there is a feedback mechanism between ghrelin, SS, and GH, which might be considered one of the possible reasons for oesophageal motility dysfunction in patients with acromegaly [9,[30][31][32]. Arosio et al indicated that GH stimulates hypothalamic SS production, as found in acromegaly, and that it may influence circulating SS levels, which might play a role in gastrointestinal motility disorders such as prolonged bowel transit in acromegaly patients [33].…”

“…Autonomic intestinal impairment and possible roles of gastrointestinal hormones (e.g. ghrelin) have been postulated to explain the motility dysfunctions [8,9]. However, the influence of acromegaly on gastrointestinal system motility and the pathological mechanisms involved are still not clarified.…”