title: Intranasal administration of neostigmine potentiates both intravenous and intranasal growth hormone (GH)-releasing hormone-induced GH release in short children.
abstract: 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 microgram/kg) or intranasally (inGHRH; 10 micrograms/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 micrograms/L.h; P less than 0.03] and potentiated the somatotroph response to ivGHRH (inNS with ivGHRH vs. ivGHRH, 1316 +/- 183.0 vs. 644.9 +/- 154.5 micrograms/L.h; P less than 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 micrograms/L.h; P less than 0.03). Administration of inNS induced a GH rise similar to that occurring after inGHRH (AUC, 239.2 +/- 69.5 micrograms/L.h) and markedly increased the inGHRH-induced GH response (482.4 +/- 103.6 micrograms/L.h; P less than 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 micrograms/kg) is able to induce a GH rise similar to that induced by ivGHRH alone (1 microgram/kg), suggesting the potential usefulness of this combination cocktail and route of administration for the treatment of short stature.
authors.affiliation: Department of Clinical Pathophysiology, University of Turin, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Ghigo
authors.forename: M
authors.initials: M
authors.lastname: Procopio
authors.forename: J
authors.initials: J
authors.lastname: Bellone
authors.forename: E
authors.initials: E
authors.lastname: Mazza
authors.forename: M
authors.initials: M
authors.lastname: Mucci
authors.forename: M F
authors.initials: MF
authors.lastname: Boghen
authors.forename: E E
authors.initials: EE
authors.lastname: Müller
authors.forename: F
authors.initials: F
authors.lastname: Camanni
mesh_terms: D000281:Administration, Intranasal; D000293:Adolescent; D002648:Child; D004357:Drug Synergism; D005260:Female; D006130:Growth Disorders / Q000097:blood* / Q000188:drug therapy; D013007:Growth Hormone-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007262:Infusions, Intravenous; D007700:Kinetics; D008297:Male; D009388:Neostigmine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D009388:Neostigmine; D013007:Growth Hormone-Releasing Hormone