Abstracts

The hypothalamo-pituitary system is innervated by cholinergic fibers and activation of the neuronal nicotinic acetylcholine receptors (nAChRs) modulates the release of anterior pituitary hormones. Mutations of nAChRs subunits are linked to autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), a syndrome characterized by clusters of nocturnal frontal seizures with no overt endocrinological manifestations. Here we assessed the effect of central cholinergic activation on the release of anterior pituitary hormones in individuals with ADNFLE., Thirteen subjects with the [alpha]4-Ser248Phe mutation (4 male, mean age 43.2 [plusmn] 16.8) and 41 healthy volunteers (24 male, mean age 36.2 [plusmn] 12.2) were studied. Serum levels of GH, LH, FSH, PRL, TSH, thyroxine and cortisol were measured at baseline, 30 and 60 minutes after infusion of physostigmine., In controls, cholinergic activation increased the serum levels of GH (mean change + 993%, P[lt]0.001), PRL (169%, P[lt]0.001) and reduced the levels of FSH (-7.9%, P[lt]0.002). In contrast, in subjects with the a4-Ser248Phe mutation no changes in the release of these hormones were observed (GH 104% P[gt]0.2; PRL 5.2%; P[gt]0.8, FSH - 0.8% P[gt]0.2). Physostigmine increased cortisol levels both in controls (P[lt]0.01) and in subjects with the mutation (P[lt]0.03). Between subjects repeated measure ANOVA showed a selective difference in the release of GH and PRL (time*group interaction GH P[lt]0.04; PRL P[lt]0.01) following administration of physostigmine., The [alpha]4-Ser248Phe mutation selectively affects cholinergic-mediated GH and PRL secretion, a finding that may be of pathophysiological significance given the role of somatostatin in experimental models of focal epilepsy.,