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Am J Physiol Endocrinol Metab 284: E641-E647, 2003. First published November 26, 2002; doi:10.1152/ajpendo.00421.2002
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Vol. 284, Issue 3, E641-E647, March 2003

Somatotropic axis in hypocretin-deficient narcoleptic humans: altered circadian distribution of GH-secretory events

Sebastiaan Overeem1, Simon W. Kok2, Gert Jan Lammers1, Alla A. Vein1, Marijke Frölich2, Arend E. Meinders2, Ferdinand Roelfsema3, and Hanno Pijl2

1 Department of Neurology and Clinical Neurophysiology, 2 Department of General Internal Medicine, and 3 Department of Endocrinology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands

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 ~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.

orexin; diurnal; deconvolution


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S. W. Kok, F. Roelfsema, S. Overeem, G. J. Lammers, M. Frolich, A. E. Meinders, and H. Pijl
Pulsatile LH release is diminished, whereas FSH secretion is normal, in hypocretin-deficient narcoleptic men
Am J Physiol Endocrinol Metab, October 1, 2004; 287(4): E630 - E636.
[Abstract] [Full Text] [PDF]




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