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Intranasal Administration of Neostigmine Potentiates both Intravenous and Intranasal Growth Hormone (GH)-Releasing Hormone-Induced GH Release in Short Children^*

Division of Endocrinology, Department of Clinical Pathophysiology, University of Turin Turin, Italy
The Department of Pharmacology, University of Milan (E.E.M.) Milan, Italy

Address all correspondence and requests for reprints to: Prof. Franco Camanni, Division of Endocrinology, Ospedale Molinette, corso Polonia 14. 10126 Torino, Italy.

Administration of cholinergic agonists increases both basal and GH-releasing hormone (GHRH)-induced GH secretion, probably acting via inhibition of endogenous somatostatin release. The aim of our study was to verify in two groups of children with idiopathic short stature the effect of intranasal administration of neostigmine (inNS; 3 mg), a cholinesterase inhibitor, on basal GH levels as well as on the somatotroph response to GHRH when the peptide was administered either iv (ivGHRH; 1 µg/kg) or intranasally (inGHRH; 10 µg/kg). In group A (n = 6; age, 10.6–16.0 yr) inNS induced a significant GH increase [inNS vs. saline, area under the curve (AUC; mean ± SEM), 263.7 ± 60.2 vs. 73.8 ± 3.1 µg/L·h; P < 0.03] and potentiated the somatotroph response to ivGHRH (inNS with ivGHRH vs. ivGHRH, 1316 ± 183.0 vs. 644.9 ± 154.5 µg/L·h; P < 0.03). In group B (n = 6; age, 11.5–15.9 yr) ivGHRH induced a GH rise clearly higher than that induced by inGHRH (604.2 ± 154.3 vs. 137.1 ± 28.2 µg/L·h; P < 0.03). Administration of inNS induced a GH rise similar to that occurring after inGHRH (AUC, 239.2 ± 69.5 µg/L·h) and markedly increased the in-GHRH-induced GH response (482.4 ± 103.6 µg/L·h; P < 0.05 and 0.03 vs. inNS and inGHRH, respectively), so that it overlapped with that induced by ivGHRH alone. In conclusion, cholinergic agonists such as neostigmine are able to increase both basal and GHRH-induced GH secretion in short children even when given intranasally. Combined intranasal administration of neostigmine and GHRH (10 µg/kg) is able to induce a GH rise similar to that induced by ivGHRH alone (1 µg/kg), suggesting the potential usefulness of this combination cocktail and route of administration for the treatment of short stature.

^* This work was supported in part by a grant from the Ministero della Pubblica Istruzione.

Received June 28, 1990.