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  • Author: F. CAVAGNINI x
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F. CAVAGNINI and M. PERACCHI

SUMMARY

The effect of reserpine on growth hormone (GH) secretion induced by insulin hypoglycaemia and by arginine infusion was studied in ten normal subjects and ten hyperthyroid patients. In both groups of subjects, oral reserpine administration resulted in a reduction of GH response to hypoglycaemia, but caused no significant change of GH release after arginine infusion. These results strongly support the theory of an adrenergic control of GH secretion and indicate that arginine stimulates GH secretion in a different way from insulin and independently of catecholamines.

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F. CAVAGNINI and R. LITTA-MODIGNANI

SUMMARY

The daily rhythm of plasma tyrosine was studied in obese subjects during total fasting, because of the relative constancy of the metabolic processes in this state. The plasma levels of tyrosine showed circadian fluctuations which were similar, although less pronounced, to those observed by other authors. The lowest values occurred at 03.00 h and the highest at 08.00 h with a second rise at 19.00 h.

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F Pecori Giraldi, E Marini, E Torchiana, P Mortini, A Dubini and F Cavagnini

Desmopressin (DDAVP), an arginine vasopressin analogue, markedly stimulates ACTH secretion in patients with Cushing's disease, in contrast to its minimal effect in normal subjects. However, little is known about the mechanisms underlying this action and it appeared to be of interest to evaluate the effect of DDAVP on ACTH-secreting pituitary adenomas in vitro, in comparison with its effect in the same patients in vivo. Pituitary adenomas from 14 patients with Cushing's disease were incubated with DDAVP, corticotrophin-releasing hormone (CRH) and DDAVP together with vasopressin receptor antagonists or CRH. Incubation with DDAVP induced a modest dose-dependent increase in ACTH concentrations which appeared maximal at 10 nM. CRH stimulated ACTH to a greater extent compared with DDAVP and potentiated the effect of DDAVP alone. The DDAVP-induced ACTH increase appeared blunted by vasopressin V(2) and V(3) receptor antagonists. V(3) receptor gene expression was detected by RT-PCR in all adenoma samples except for two which were not responsive to DDAVP in vitro but responsive to the peptide in vivo. Surprisingly, no difference in the in vitro ACTH secretory response was observed between in vivo DDAVP-responsive (ACTH peak>150% baseline) and -unresponsive (ACTH peak<120% baseline) patients, suggesting that the pituitary adenoma is not the sole mediator of the ACTH-releasing effect of DDAVP. In conclusion, the marked stimulatory effect of DDAVP observed in patients with Cushing's disease appears to be mainly dependent on an extrapituitary action, possibly the inhibition of a corticotrophin release-inhibitory factor.

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F. CAVAGNINI, M. PERACCHI, G. SCOTTI, U. RAGGI, A. E. PONTIROLI and R. BANA

SUMMARY

The effect of both oral and intravenous administration of l-DOPA on growth hormone (GH) secretion was studied in a group of normal volunteers: a significant rise of serum GH levels was observed in both cases.

Growth hormone release in response to insulin hypoglycaemia and to arginine infusion was evaluated in a group of Parkinsonian patients before and after 25 days' treatment with l-DOPA plus a DOPA-decarboxylase inhibitor. In addition, GH response to the above stimuli was studied in a group of patients who had been under treatment for more than 6 months with l-DOPA alone. In untreated Parkinsonian patients, GH response to insulin hypoglycaemia was at the lower limit of normal range while arginine-induced GH release was significantly reduced. Treatment with l-DOPA did not increase GH responses. Some possible interpretations of the results are discussed.

The findings support the possibility that dopamine plays a role in the physiological regulation of GH secretion, as in the case of luteinizing hormone, follicle-stimulating hormone and prolactin release.

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AE Rigamonti, AI Pincelli, B Corra, R Viarengo, SM Bonomo, D Galimberti, M Scacchi, E Scarpini, F Cavagnini and EE Muller

Ghrelin, a novel endogenous ligand for the GH secretagogue receptor, has been reported to stimulate GH secretion and food intake in both humans and other animals. Interestingly, recent data indicate that ghrelin is up- and down-regulated in anorexia nervosa (AN) and obesity, which are also known to be accompanied by increased and reduced GH levels respectively. Ageing is associated with a gradual but progressive reduction in GH secretion, and by alterations in appetite and food intake. The role of ghrelin in the decline of somatotroph function and the anorexia of ageing is unknown. To investigate the influence of age on circulating levels of ghrelin, a total of 19 young and old normal weight subjects (Y-NW, n=12; O-NW, n=7), six patients with active AN (A-AN), and seven patients with morbid obesity (OB) were studied. In addition to fasting plasma ghrelin concentrations, baseline serum TSH, IGF-I and insulin levels were measured. Mean plasma ghrelin concentrations in A-AN or OB were higher and lower respectively than those present in Y-NW. Interestingly, mean plasma ghrelin concentrations in O-NW were significantly lower than those present in Y-NW and superimposable on those of OB. The mean fasting plasma ghrelin concentrations in all groups of subjects were negatively correlated with body mass index and serum insulin levels, but not with TSH and IGF-I levels. This study provides evidence of an age-related decline of plasma ghrelin concentrations, which might explain, at least partially, the somatotroph dysregulation and the anorexia of the elderly subject.