Association of a nicotinic receptor mutation with reduced height and blunted physostigmine-stimulated growth hormone release.
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.


OBJECTIVE
Our aim was to assess the effect of a mutation in the alpha4 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 alpha4-Ser248Phe mutation (four male, age 43.2 +/- 16.8 yr) were studied. Serum levels of GH, LH, FSH, prolactin, TSH, free T(4), 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/m(2), 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.
Department of Medicine, Austin Hospital, The University of Melbourne, Heidelberg, Victoria 3084 Australia.
Marco
M
Fedi
Leon A
LA
Bach
Samuel F
SF
Berkovic
John O
JO
Willoughby
Ingrid E
IE
Scheffer
David C
DC
Reutens
D000293:Adolescent; D000328:Adult; D000368:Aged; D001827:Body Height / Q000235:genetics*; D015992:Body Mass Index; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006130:Growth Disorders / Q000097:blood / Q000235:genetics*; D019382:Human Growth Hormone / Q000097:blood / Q000502:physiology*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008875:Middle Aged; D010830:Physostigmine / Q000494:pharmacology; D017354:Point Mutation; D011388:Prolactin / Q000097:blood; D011978:Receptors, Nicotinic / Q000235:genetics*; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood
D002800:Cholinesterase Inhibitors; D011978:Receptors, Nicotinic; D019382:Human Growth Hormone; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D013972:Thyrotropin; D010830:Physostigmine; D013974:Thyroxine; D006854:Hydrocortisone