CLINICAL STUDY Ghrelin administration affects circulating pituitary and gastro-entero-pancreatic hormones in acromegaly M Arosio 1,4 , C L Ronchi 1 , C Gebbia 2 , S Pizzinelli 2 , D Conte 2 , V Cappiello 1 , P Epaminonda 1,4 , B M Cesana 3 , P Beck-Peccoz 1 and M Peracchi 2 1 Institute of Endocrine Sciences, 2 Department of Medical Sciences and 3 Epidemiology Unit, University of Milan, Ospedale Maggiore IRCCS, via F Sforza, 35, Milan, Italy and 4 Operative Unit of Endocrinology,Ospedale S Giuseppe-Fatebenefratelli, AFaR, via S Vittore, 12, 20100 Milan, Italy (Correspondence should be addressed to M Arosio, UO Endocrinologia, Ospedale S Giuseppe, Via S Vittore, 12, 20123 Milan, Italy; Email: maura.arosio@unimi.it) Abstract Objective: Ghrelin, a gut–brain peptide involved in the control of energy homeostasis, affects antero- pituitary 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 acrome- galic 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. European Journal of Endocrinology 150 27–32 Introduction Ghrelin, the recently discovered gut –brain hormone with well-known powerful growth hormone (GH)- releasing activity (1, 2), regulates energy homeostasis by increasing food intake and fat deposition (3, 4) and modulates the endocrine system by stimulating prolactin (PRL) and adrenocorticotropic hormone (ACTH) secretion in healthy human subjects (5). Its PRL-releasing activity seems to be due to a direct effect on mammosomatotroph cells (6), whereas the release of ACTH appears to be mediated by ghrelin at the hypothalamic level (6). Moreover, in the rat, ghrelin modulates gastric motility and acid secretion (7, 8), inhibits gastric emptying (7) and increases insulin and gastrin secretion (9). In healthy humans, ghrelin reduces insulin secretion (10, 11) and increases both somatostatin (SS) and pancreatic polypeptide (PP) circulating levels but does not influence plasma gastrin levels (11). All these findings suggest important links between ghrelin and other gastro-entero-pancreatic (GEP) hormones. In acromegaly, a disease characterized by persistently elevated GH concentrations, alterations in circulating levels of some GEP hormones (12, 13) and subnormal concentrations of ghrelin have been described (14, 15). It is still not known if this pathological condition modifies the pituitary and/or GEP hormone responses to pharmacological ghrelin administration. Therefore, we evaluated the effects of ghrelin administration on GH, PRL, ACTH, cortisol, insulin, glucose, SS and PP levels in patients with active acromegaly. European Journal of Endocrinology (2004) 150 27–32 ISSN 0804-4643 q 2004 Society of the European Journal of Endocrinology Online version via http://www.eje.org Downloaded from Bioscientifica.com at 06/15/2020 08:49:41AM via free access