Background: Pulsatile GH secretion from the anterior pituitary is a key mediator of human growth regulation and is affected by a number of genetic and environmental factors. Activation of neuronal nicotinic (nACh) receptors promotes GH release but the role of these receptors in growth regulation is unknown.

Aim: To assess the effect of a mutation in the in the 4 subunit of the nACh receptor on cholinergic-mediated GH release.

Methods: Forty-one healthy volunteers (24 male, age 36.2 ± 12.2, mean ± SD) and 13 subjects with the 4-Ser248Phe mutation (4 male, age 43.2 ± 16.8) were studied. Serum levels of GH, LH, FSH, PRL, TSH, FT4 and cortisol were measured at baseline and at regular intervals after infusion of physostigmine. Height and weight were recorded in all participants as well from additional family members with (n=11, 4 male) and without (n=16, 7 male) the mutation.

Results: Subjects with the mutation were shorter (1.62 ± 0.08 vs 1.72 ± 0.09 m, P<0.05) and had a greater body mass index (31 ± 6 vs 24 ± 3 kg/m², P<0.05) than healthy volunteers and non-affected members of the pedigree. In controls, physostigmine markedly increased the serum levels of GH (mean increase +732%). In contrast, the response to physostigmine was markedly blunted in subjects with the mutation (+104%, P>0.2 vs control).

Conclusions: These findings suggest a role of the nACh receptor in human growth regulation.