HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 287/4/E630    most recent 00060.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Kok, S. W. Articles by Pijl, H. Search for Related Content PubMed PubMed Citation Articles by Kok, S. W. Articles by Pijl, H.

Pulsatile LH release is diminished, whereas FSH secretion is normal, in hypocretin-deficient narcoleptic men

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

Submitted 9 February 2004 ; accepted in final form 27 May 2004

Hypocretin (orexin) peptides are involved in the regulation of energy balance and pituitary hormone release. Narcolepsy is a sleep disorder characterized by disruption of hypocretin neurotransmission. Pituitary LH secretion is diminished in hypocretin-deficient animal models, and intracerebroventricular administration of hypocretin-1 activates the hypothalamo-pituitary-gonadal axis in rats. We evaluated whether hypocretin deficiency affects gonadotropin release in humans. To this end, we deconvolved 24-h serum concentrations of LH and FSH in seven hypocretin-deficient narcoleptic males (N) and seven controls (C) matched for age, body mass index, and sex. Basal plasma concentrations of testosterone, estradiol, and sex hormone-binding globulin were similar in both groups. Mean 24-h LH concentration was significantly lower in narcolepsy patients [3.0 ± 0.4 (N) vs. 4.2 ± 0.3 (C) U/l, P = 0.01], which was primarily due to a reduction of pulsatile LH secretion [23.5 ± 1.6 (N) vs. 34.3 ± 4.9 (C) U·l^–1·24 h^–1, P = 0.02]. The orderliness of LH and FSH secretion, quantitated by the approximate entropy statistic, was greater in patients than in controls. In contrast, all other features of FSH release were similar in narcoleptic and control groups. Also, LH and FSH secretions in response to intravenous administration of 100 µg of GnRH were similar in patients and controls. These data indicate that endogenous hypocretins are involved in the regulation of the hypothalamo-pituitary-gonadal axis activity in humans. In particular, reduced LH release in the face of normal pituitary responsivity to GnRH stimulation in narcoleptic men suggests that hypocretins promote endogenous GnRH secretion.

orexin; luteinizing hormone; follicle-stimulating hormone; testosterone; estradiol; circadian rhythm; deconvolution analysis

This article has been cited by other articles:

				P. Silveyra, V. Lux-Lantos, and C. Libertun Both orexin receptors are expressed in rat ovaries and fluctuate with the estrous cycle: effects of orexin receptor antagonists on gonadotropins and ovulation Am J Physiol Endocrinol Metab, October 1, 2007; 293(4): E977 - E985. [Abstract] [Full Text] [PDF]

				P. Silveyra, P. N. Catalano, V. Lux-Lantos, and C. Libertun Impact of proestrous milieu on expression of orexin receptors and prepro-orexin in rat hypothalamus and hypophysis: actions of Cetrorelix and Nembutal Am J Physiol Endocrinol Metab, March 1, 2007; 292(3): E820 - E828. [Abstract] [Full Text] [PDF]

				G Sun, Z Tian, Y Yao, H Li, and T Higuchi Central and/or peripheral immunoreactivity of orexin-A in pregnant rats and women J. Mol. Endocrinol., February 1, 2006; 36(1): 131 - 138. [Abstract] [Full Text] [PDF]