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Am J Physiol Endocrinol Metab (November 26, 2002). doi:10.1152/ajpendo.00421.2002
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Articles in PresS, published online ahead of print November 26, 2002
Am J Physiol Endocrinol Metab, 10.1152/ajpendo.00421.2002
Submitted on October 1, 2002
Accepted on November 22, 2002

The 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 Frolich2, Arend E. Meinders2, Ferdinand Roelfsema3, and Hanno Pijl2*

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

* To whom correspondence should be addressed. E-mail: h.pijl{at}lumc.nl.

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 hours in narcoleptics. Furthermore, hypocretins may inhibit pituitary GH release. We assessed the function of the somatotropic axis in narcolepsy, by deconvolving 24- hour (10 minute sampling interval) plasma GH concentration profiles in 7 hypocretindeficient narcoleptic patients and in 7 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 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 GHRH release in narcoleptic patients to simultaneously cause daytime GH release and promote their propensity to fall asleep during the day.




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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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