Somatotropic axis in hypocretin-deficient narcoleptic humans: altered circadian distribution of GH-secretory events.
Narcolepsy is a sleep disorder caused by impaired hypocretin (orexin) neurotransmission. Growth hormone (GH) secretion may be altered in narcolepsy for various reasons. Slow-wave sleep episodes, which are closely associated with GH-secretory events, are more randomly dispersed over 24 h in narcoleptics. Furthermore, hypocretins may inhibit pituitary GH release. We assessed the function of the somatotropic axis in narcolepsy by deconvolving 24-h (10-min sampling interval) plasma GH concentration profiles in seven hypocretin-deficient narcoleptic patients and in seven healthy controls matched for age, sex, and body weight. Both basal and pulsatile GH secretion rate and secretagogue-induced GH release were similar in patients and controls. However, narcoleptics secreted approximately 50% of their total production during the daytime, whereas controls secreted only 25% during the day. Also, the GH output pattern of narcoleptics was significantly less regular. We propose that hypocretin deficiency disrupts the circadian distribution of hypothalamic GH-releasing hormone release in narcoleptic patients to simultaneously cause daytime GH release and promote their propensity to fall asleep during the day.
Overeem
Sebastiaan
S
Department of Neurology and Clinical Neurophysiology, Leiden University Medical Center, The Netherlands.
Kok
Simon W
SW
Lammers
Gert Jan
GJ
Vein
Alla A
AA
Frölich
Marijke
M
Meinders
Arend E
AE
Roelfsema
Ferdinand
F
Pijl
Hanno
H
D000328:Adult; D000368:Aged; D002352:Carrier Proteins; D002940:Circadian Rhythm; D013006:Growth Hormone / Q000097:blood* / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D006801:Humans; D007275:Injections, Intravenous; D047908:Intracellular Signaling Peptides and Proteins; D008661:Metabolism, Inborn Errors / Q000150:complications / Q000378:metabolism; D008875:Middle Aged; D009290:Narcolepsy / Q000209:etiology / Q000378:metabolism*; D009479:Neuropeptides / Q000172:deficiency*; D000068797:Orexins; D012016:Reference Values; D012890:Sleep
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone