Abstracts

Rationale: Mutations of the neuronal nicotinic acetylcholine receptors (nAChRs) subunits have been linked to autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). The hypothalamo-pituitary system is densely innervated by cholinergic fibers and activation of the nAChRs modulates the release of anterior pituitary hormones. Here we studied the effect of central cholinergic activation on the release of anterior pituitary hormones in individuals affected by ADNFLE.Methods: Thirteen subjects affected by the α4-Ser248Phe mutation (4 male, mean age 43.2 ± 16.8) and 41 healthy volunteers (24 male, mean age 36.2 ± 12.2) were studied. Serum levels of GH, LH, FSH, PRL, TSH, thyroxine and cortisol were measured at baseline, at 30 and 60 minutes after infusion of physostigmine. Anthropometric measurements in controls, subjects with ADNFLE and in additional family members without the mutation were also obtained.Results: Cholinergic activation increased the serum levels of GH, PRL and reduced the levels of FSH in controls but not in subjects with the α4-Ser248Phe mutation. Subjects with the mutation were shorter and had a greater body mass index than unaffected members of the pedigree.Conclusions: This study demonstrates that the α4-Ser248Phe mutation selectively affects cholinergic-mediated GH and PRL secretion. It is possible that the neuroendocrine deficit partially contributes to the clinical phenotype of ADNFLE. In addition, these findings suggest a role of the nACh receptor in human growth regulation.