This Article Full Text Full Text (PDF) All Versions of this Article: 93/2/634    most recent Author Manuscript (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Fedi, M. Articles by Reutens, D. C. Search for Related Content PubMed PubMed Citation Articles by Fedi, M. Articles by Reutens, D. C. Pubmed/NCBI databases Gene GEO Profiles HomoloGene Nucleotide Protein UniGene Compound via MeSH Substance via MeSH Medline Plus Health Information Growth Disorders Hazardous Substances DB HYDROCORTISONE LEVOTHYROXINE MENOTROPINS PHYSOSTIGMINE Related Collections Neuroendocrinology and Pituitary Pediatric Endocrinology

Association of a Nicotinic Receptor Mutation with Reduced Height and Blunted Physostigmine-Stimulated Growth Hormone Release

Department of Medicine, Austin Hospital (M.F., S.F.B., I.E.S., D.C.R.), The University of Melbourne, Heidelberg, Victoria 3084 Australia; Department of Medicine, Alfred Hospital (L.A.B.), Monash University, Prahran, Victoria 3181, Australia; Centre for Neuroscience (J.O.W.), Flinders University, Adelaide, South Australia 5001, Australia; and Southern Clinical School, Monash University (D.C.R., M.F.), Clayton, Victoria 3168, Australia

Address all correspondence and requests for reprints to: David C. Reutens, M.D., FRACP, Southern Clinical School, Monash Medical Centre, 246 Clayton Road, Clayton, Victoria 3168, Australia. E-mail: David.Reutens{at}med.monash.edu.au.

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 acetylcholine (nACh) receptors promotes GH release, but the role of these receptors in growth regulation is unknown.

Aim: Our aim was to assess the effect of a mutation 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 yr, mean ± SD) and 13 subjects with the 4-Ser248Phe mutation (four male, age 43.2 ± 16.8 yr) were studied. Serum levels of GH, LH, FSH, prolactin, TSH, free T₄, and cortisol were measured at baseline and at regular intervals after infusion of physostigmine. Height and weight were recorded in all participants as well as from additional family members with (n = 11, four male) and without (n = 16, seven 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 unaffected 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.