, Volume 8, Issue 4, pp 232–248 | Cite as

Hormones, hormonal agents, and neuropeptides involved in the neuroendocrine regulation of sleep in humans

  • Grigorios KotronoulasEmail author
  • Antonios Stamatakis
  • Fotini Stylianopoulou


Sleep is an essential ubiquitous biological process, a periodical state of quiescence in which there is minimal processing of sensory information and no interaction with conspecifics or the environment. Despite relevant research on sleep structure and testing of numerous endogenous sleep-affecting chemicals, questions as to the precise mechanisms and functions of sleep remain without satisfactory responses. The purpose of this review is to report on current evidence as regards the effect of several endogenous and exogenous hormones, hormonal agents, and neuropeptides on sleep onset or wake process, when administered in humans in specific doses and via different routes. The actions of several peptides are presented in detail. Some of them (growth hormone releasing hormone, ghrelin, galanin, neuropeptide Y) seem to promote sleep, whereas others (corticotropin, somatostatin) impair its continuity.


Ghrelin GHRH Hormones Melatonin NPY Neuroendocrine regulation Neuropeptides Sleep Sleep disorders Wakefulness 


  1. 1.
    Greenspan RJ, Tononi G, Cirelli C, Shaw PJ, 2001 Sleep and the fruit fly. Trends Neurosci 24: 142–145.PubMedCrossRefGoogle Scholar
  2. 2.
    “The Regulation of Sleep”, 2000 Borbély AA, Hayaishi O, Sejnowski TJ, Altman JS (eds). HFSP, Strasbourg, France.Google Scholar
  3. 3.
    Porkka-Heiskanen T, Alanko L, Kalinchuk A, Stenberg D, 2002 Adenosine and Sleep. Sleep Med Rev 6: 321–332.PubMedCrossRefGoogle Scholar
  4. 4.
    Krueger JM, Majde JA, Obál F Jr, 2003 Sleep in host defense. Brain Behav Immun 17: S41–S47.PubMedCrossRefGoogle Scholar
  5. 5.
    Akerstedt T, Nilsson PM, 2003 Sleep as restitution: an introduction. J Intern Med 254: 6–12.PubMedCrossRefGoogle Scholar
  6. 6.
    Sateia MJ, Santulli RB, 1998 Sleep in palliative care. In: Doyle O, Hanks GWC, MacDonald N (eds). Oxford Textbook of Palliative Medicine (2nd Ed). New York: Oxford University Press; Chapter 8, pp, 731–746.Google Scholar
  7. 7.
    Buckley TM, Schatzberg AF, 2005 On the interactions of the HPA axis and sleep: Normal HPA axis and rhythm, exemplary sleep disorders. J Clin Endocrinol Metab 90: 3106–3114.PubMedCrossRefGoogle Scholar
  8. 8.
    Borbély AA, 1982 A two process model of sleep regulation [Abstract]. Hum Neurobiol 1: 195–204.PubMedGoogle Scholar
  9. 9.
    Borbély AA, Achermann P, 1999 Sleep homeostasis and models of sleep regulation. J Biol Rhythms 14: 557–568.PubMedGoogle Scholar
  10. 10.
    Steiger A, 2003 Sleep and endocrinology. J Intern Med 254: 13–22.PubMedCrossRefGoogle Scholar
  11. 11.
    Steiger A, 2007 Neurochemical regulation of sleep. J Psychiatr Res 41: 537–552.PubMedCrossRefGoogle Scholar
  12. 12.
    Antonijevic IA, Murck H, Frieboes RM, et al, 1999 On the gender differences in sleep-endocrine regulation in young normal humans. Neuroendocrinol 70: 280–287.CrossRefGoogle Scholar
  13. 13.
    Obál F Jr, Krueger JM, 2004 GHRH and sleep. Sleep Med Rev 8: 367–377.PubMedCrossRefGoogle Scholar
  14. 14.
    Steiger A, Guldner J, Hemmeter U, et al, 1992 Effects of growth hormone-releasing hormone and somatostatin on sleep EEG and nocturnal hormone secretion in male controls. Neuroendocrinol 56: 566–573.CrossRefGoogle Scholar
  15. 15.
    Marshall L, Mölle M, Böschen G, et al, 1996 Greater efficacy of episodic than continuous growth hormone-releasing hormone (GHRH) administration in promting slow-wave sleep (SWS). J Clin Endocrinol Metab 81: 1009–1013.PubMedGoogle Scholar
  16. 16.
    Obál F Jr, Krueger JM, 2003 Biochemical regulation of non-rapideye-movement sleep. Front Biosci 8: d520–550.PubMedCrossRefGoogle Scholar
  17. 17.
    Kupfer DJ, Jarrett DB, Ehlers CL, 1991 The effect of GRF on the EEG sleep of normal males. Sleep 14: 87–88.PubMedGoogle Scholar
  18. 18.
    Mathias S, Held K, Ising M, et al, 2007 Systemic growth hormone-releasing hormone (GHRH) impairs sleep in healthy young women. Psychoneuroendocrinol 32: 1021–1027.CrossRefGoogle Scholar
  19. 19.
    Kerkhofs M, Van Cauter E, Van Onderbergen A, et al, 1993 Sleep-promoting effects of growth hormone-releasing hormone in normal men. Am J Physiol 264: E594–E598.PubMedGoogle Scholar
  20. 20.
    Schier T, Guldner J, Colla M, Holsboer F, Steiger A, 1997 Changes in sleep-endocrine activity after growth hormone-releasing hormone depend on time of administration. J Neuroendocrinol 9: 201–205.PubMedCrossRefGoogle Scholar
  21. 21.
    Steiger A, 2003 Sleep and endocrine regulation. Front Biosci 8: s358–s376.PubMedCrossRefGoogle Scholar
  22. 22.
    Perras B, Marshall L, Köhler G, Born J, Fehm HL, 1999 Sleep and endocrine changes after intranasal administration of growth hormone-releasing hormone in young and aged humans. PNEC 24: 743–757.Google Scholar
  23. 23.
    Schiissler P, Yassouridis A, Uhr M, et al, 2006 Growth hormone-releasing hormone and corticotropin-releasing hormone enhance non-rapid-eye-movement sleep after sleep deprivation. Am J Physiol Endocrinol Metab 291: E549–556.CrossRefGoogle Scholar
  24. 24.
    Guldner J, Schier T, Friess E, et al, 1997 Reduced efficacy of growth hormone-releasing hormone in modulating sleep endocrine activity in the elderly. Neurobiol Aging 18: 491–495.PubMedCrossRefGoogle Scholar
  25. 25.
    Antonijevic IA, Murck H, Frieboes RM, Barthelmes J, Steiger A, 2000 Sexually dimorphic effects of GHRH on sleep endocrine activity in patients with depression and normal controls — part I: the sleep EEG. Sleep Research Online 3: 5–13.PubMedGoogle Scholar
  26. 26.
    Obál Jr F, Payne L, Kapas L, et al, 1991 Inhibition of growth hormone-releasing factor suppresses both sleep and growth hormone secretion in the rat. Brain Res 557: 149–153.PubMedCrossRefGoogle Scholar
  27. 27.
    Zhang J, Obál F Jr, Zheng T, et al, 1999 Intrapreoptic microinjection of GHRH or its antagonist alters sleep in rats. J Neurosci 19: 2187–2194.PubMedCrossRefGoogle Scholar
  28. 28.
    Obál F Jr, Payne L, Opp M, et al, 1992 Growth hormone-releasing hormone antibodies suppress sleep and prevent enhancement of sleep after sleep deprivation. Am J Physiol 263: R1078–R1085.PubMedGoogle Scholar
  29. 29.
    Merriam GR, Schwartz RS, Vitiello MV, 2003 Growth hormone-releasing hormone and growth hormone secretagogues in normal aging. Endocrine 22: 41–48.PubMedCrossRefGoogle Scholar
  30. 30.
    Doga M, Bonadonna S, Burattin A, Giustina A, 2001 Ectopic secretion of growth hormone-releasing hormone (GHRH) in neuroendocrine tumors: relevant clinical aspects. Ann Oncol 12: Suppl 2: S89–S94.PubMedCrossRefGoogle Scholar
  31. 31.
    Kojima M, Hosoda H, Date Y, et al, 1999 Ghrelin is a growth hormone-releasing acylated peptide from stomach. Nature 402: 656–660.CrossRefGoogle Scholar
  32. 32.
    Ghigo E, Broglio F, Arvat E, et al, 2005 Ghrelin: more than a natural GH secretagogue and/or an orexigenic factor. Clin Endocrinol 62: 1–17.CrossRefGoogle Scholar
  33. 33.
    Korbonits M, Goldstone AP, Gueorguiev M, Grossman AB, 2004 Ghrelin — a hormone with multiple functions. Front Neuroendocrinol 25: 27–68.PubMedCrossRefGoogle Scholar
  34. 34.
    van der Lely AJ, Tschop M, Heiman ML, Ghigo E, 2004 Biological, physiological, pathophysiological, and pharmacological aspects of ghrelin. Endocrin Rev 25: 426–457.CrossRefGoogle Scholar
  35. 35.
    Arvat E, Maccario M, Di Vito L, et al, 2001 Endocrine activities of ghrelin, a natural growth hormone secretagogue (GHS), in humans: comparison and interactions with hexarelin, a nonnatural peptidyl GHS, and GH-releasing hormone. J Clin Endocrinol Metab 86: 1169–1174.PubMedPubMedCentralGoogle Scholar
  36. 36.
    Weikel JC, Wichniak A, Ising M, et al, 2003 Ghrelin promotes slow-wave sleep in humans. Am J Physiol Endocrinol Metab 284: E407–E415.PubMedCrossRefGoogle Scholar
  37. 37.
    Schuessler P, Uhr M, Ising M, et al, 2005 Nocturnal ghrelin levels — relationship to sleep EEG, the levels of growth hormone, ACTH and cortisol — and gender differences. J Sleep Res 14: 329–336.PubMedCrossRefGoogle Scholar
  38. 38.
    Kluge M, Schüssler P, Zuber V, Yassouridis A, Steiger A, 2007 Ghrelin administered in the early morning increases secretion of cortisol and growth hormone without affecting sleep. Psychoneuroendocrinol 32: 287–292.CrossRefGoogle Scholar
  39. 39.
    Copinschi G, Leproult R, Van Onderbergen A, et al, 1997 Prolonged oral treatment with MK-677, a novel growth hormone secretagogue, improves sleep quality in man. Neuroendocrinol 66: 278–286.CrossRefGoogle Scholar
  40. 40.
    Frieboes RM, Murck H, Antonijevic IA, Steiger A, 1999 Effects of growth hormone-releasing peptide-6 on the nocturnal secretion of GH, ACTH and cortisol and on the sleep EEG in man: role of routes of administration. J Neuroendocrinol 11: 473–478.PubMedCrossRefGoogle Scholar
  41. 41.
    Moreno-Reyes R, Kerkhofs M, L’Hermite-Baleriaux M, et al, 1998 Evidence against a role for the growth hormone-releasing peptide axis in human slow-wave sleep regulation. Am J Physiol 274: E779–E784.PubMedGoogle Scholar
  42. 42.
    Frieboes RM, Antonijevic IA, Held K, et al, 2004 Hex-arelin decreases slow-wave sleep and stimulates the secretion of GH, ACTH, cortisol and prolactin during sleep in healthy volunteers. Psychoneuroendocrinol 29: 851–860.CrossRefGoogle Scholar
  43. 43.
    Simi L, Pinzani P, Raggi CC, et al, 2007 Influence of 17q gain and promoter polymorphisms on mRNA expression of somatostatin receptor type 2 in neuroblastoma. Clin Chim Acta 384: 149–154.PubMedCrossRefGoogle Scholar
  44. 44.
    Frieboes RM, Murck H, Schier T, Holsboer F, Steiger A, 1997 Somatostatin impairs sleep in elderly human subjects [Abstract]. Neuropsychopharmacol 16: 339–345.CrossRefGoogle Scholar
  45. 45.
    Steiger A, Weikel J, Held K, Schmid D, Ziegenbein M, 2002 Arginine improves sleep in elderly men [Abstract]. Sleep 25: A203.Google Scholar
  46. 46.
    Ziegenbein M, Murck H, Künzel H, Held K, Steiger A, 1999 Sleep-endocrine effects of growth hormone-releasing hormone (GHRH) in patients with obsessive-compulsive disorder (OCD). Pharmacopsychiatry 32: 220.Google Scholar
  47. 47.
    de Lecea L, Bourgin P, 2008 Neuropeptide interactions and REM sleep: a role for Urotensin II? Peptides 29: 845–851.PubMedCrossRefGoogle Scholar
  48. 48.
    de Lecea L, 2005 Cortistatin: a natural somatostatin analog. J Endocrinol Invest 28: 10–14.PubMedGoogle Scholar
  49. 49.
    van der Klaauw AA, Pereira AM, van Kralingen KW, Rabe KF, Romijn JA, 2008 Somatostatin analog treatment is associated with an increased sleep latency in patients with long-term biochemical remission of acromegaly. Growth Horm IGF Res 18: 446–453.PubMedCrossRefGoogle Scholar
  50. 50.
    Holsboer F, von Bardeleben U, Steiger A, 1988 Effects of intravenous corticotropin-releasing hormone upon sleep-related growth hormone surge and sleep EEG in man. Neuroendocrinol 48: 32–38.CrossRefGoogle Scholar
  51. 51.
    Steiger A, Holsboer F, 1997. Neuropeptides and human sleep. Sleep 20: 1038–1052.PubMedGoogle Scholar
  52. 52.
    Antonijevic IA, Murck H, Frieboes RM, et al, 1999 Hyporesponsiveness of the pituitary to CRH during slow wave sleep is not mimicked by systemic GHRH. Neuroendocrinol 69: 88–96.CrossRefGoogle Scholar
  53. 53.
    Vgontzas AN, Bixler EO, Wittman AM, et al, 2001 Middle-aged men show higher sensitivity of sleep to the arousing effects of corticotropin-releasing hormone than young men: clinical implications. J Clin Endocrinol Metab 86: 1489–1495.PubMedCrossRefGoogle Scholar
  54. 54.
    Chang FC, Opp MR, 2001 Corticotropin-releasing hormone (CRH) as a regulator of waking. Neurosci Biobehav Rev 25: 445–453.PubMedCrossRefGoogle Scholar
  55. 55.
    Held K, Kunzel H, Ising M, et al, 2004 Treatment with the CRH1-receptorantagonist R121919 improves sleep-EEG in patients with depression. J Psychiatr Res 38: 129–136.PubMedCrossRefGoogle Scholar
  56. 56.
    Antonijevic I, 2007. HPA axis and sleep: identifying subtypes of major depression. Stress 11: 15–27.PubMedCrossRefGoogle Scholar
  57. 57.
    Liu Z, Zhu F, Wang G, et al, 2007 Association study of corticotropin-releasing hormone receptor1 gene polymorphisms and antidepressant response in major depressive disorders. Neurosci Lett 414: 155–158.PubMedCrossRefGoogle Scholar
  58. 58.
    Fehm HL, Späth-Schwalbe E, Pietrowsky R, et al, 1993 Entrainment of nocturnal pituitary-adrenocortical activity to sleep processes in man — a hypothesis. Exp Clin Endocrinol 101: 267–276.PubMedCrossRefGoogle Scholar
  59. 59.
    Born J, Hansen K, Marshall L, et al, 1999 Timing the end of nocturnal sleep. Nature 397: 29–30.PubMedCrossRefGoogle Scholar
  60. 60.
    Steiger A, 2002. Sleep and the hypothalamo-pituitary-adrenocortical system. Sleep Med Rev 6: 125–138.PubMedCrossRefGoogle Scholar
  61. 61.
    Alexis MN, Stylianopoulou F, Kitraki E, Sekeris CE, 1983 The distribution and properties of the glucocorticoid receptor from rat brain and pituitary. J Biol Chem 258: 4710–4714.PubMedGoogle Scholar
  62. 62.
    Friess E, Wiedemann K, Steiger A, et al, 1995 The hypothalamic-pituitary-adrenocortical system and sleep in man. Adv Neuroimmunol 5: 111–125.PubMedCrossRefGoogle Scholar
  63. 63.
    Bohlhalter S, Murck H, Holsboer F, Steiger A, 1997 Cortisol enhances non-REM sleep and growth hormone secretion in elderly subjects. Neurobiol Aging 18: 423–429.PubMedCrossRefGoogle Scholar
  64. 64.
    Born J, DeKloet ER, Wenz H, Kern W, Fehm HL, 1991 Gluco- and antimineralocorticoid effects on human sleep: a role of central corticosteroid receptors. Am J Physiol 260: E183–188.PubMedCrossRefGoogle Scholar
  65. 65.
    Friess E, von Bardeleben U, Wiedemann K, Lauer C, Holsboer F, 1994 Effects of pulsatile cortisol infusion on sleep-EEG and nocturnal growth hormone release in healthy men. J Sleep Res 3: 73–79.PubMedCrossRefGoogle Scholar
  66. 66.
    Friess E, Tagaya H, Grethe C, Trachsel L, Holsboer F, 2004 Acute cortisol administration promotes sleep intensity in man. Neuropsychopharmacol 29: 598–604.CrossRefGoogle Scholar
  67. 67.
    Schmid DA, Brunner H, Lauer CJ, et al, 2008 Acute cortisol administration increases sleep depth and growth hormone release in patients with major depression. J Psychiatr Res 42: 991–999.PubMedCrossRefGoogle Scholar
  68. 68.
    Gillin JC, Jacobs LS, Fram DH, Snyder F, 1972 Acute effect of a glucocorticoid on normal human sleep [Abstract]. Nature 237: 398–399.PubMedCrossRefGoogle Scholar
  69. 69.
    Gillin JC, Jacobs LS, Snyder F, et al, 1974 Effects of ACTH on the sleep of normal subjects and patients with Addison’s disease. Neuroendocrinology 15: 21–31.PubMedCrossRefGoogle Scholar
  70. 70.
    Krieger DT, Glick SM, 1974 Sleep EEG stages and plasma growth hormone concentration in states of endogenous and exogenous hypercortisolemia or ACTH elevation. J Clin Endocrinol Metab 39: 986–1000.PubMedCrossRefGoogle Scholar
  71. 71.
    Shipley JE, Schteingart DE, Tandon R, et al, 1992 Sleep architecture and sleep apnea in patients with Cushing’s disease. Sleep 15: 514–518.PubMedCrossRefGoogle Scholar
  72. 72.
    Steiger A 2007 Neuroendocrinology of Sleep. In: Lajtha A, Blaustein JD (Eds). Handbook of Neurochemistry and Molecular Neurobiology, Plenum Press, New York, pp, 897–926.Google Scholar
  73. 73.
    Antonijevic IA, Steiger A, 2003 Depression-like changes of the sleep-EEG during high dose corticosteroid treatment in patients with multiple sclerosis. PNEC 28: 780–795.Google Scholar
  74. 74.
    Buckley T, Duggal V, Schatzberg AF, 2008 The acute and post-discontinuation effects of a glucocorticoid receptor (GR) antagonist probe on sleep and the HPA axis in chronic insomnia: a pilot study. J Clin Sleep Med 4: 235–241.PubMedPubMedCentralGoogle Scholar
  75. 75.
    Murck H, Held K, Ziegenbein M, et al, 2004 Intravenous administration of the neuropeptide galanin has fast antidepressant efficacy and affects the sleep EEG. PNEC 29: 1205–1211.Google Scholar
  76. 76.
    Murck H, Antonijevic IA, Frieboes RM, et al, 1999 Galanin has REM-sleep deprivation-like effects on the sleep EEG in healthy young men. J Psychiatr Res 33: 225–232.PubMedCrossRefGoogle Scholar
  77. 77.
    Unschuld PG, Ising M, Erhardt A, et al, 2008 Polymorphisms in the galanin gene are associated with symptom-severity in female patients suffering from panic disorder. J Affect Disord 105: 177–184.PubMedCrossRefGoogle Scholar
  78. 78.
    Gallopin T, Luppi PH, Cauli B, et al, 2005 The endogenous somnogen adenosine excites a subset of sleep-promoting neurons via A2A receptors in the ventrolateral preoptic nucleus. Neuroscience 134: 1377–1390.PubMedCrossRefGoogle Scholar
  79. 79.
    Rétey JV, Adam M, Honegger E, et al, 2005 A functional genetic variation of adenosine deaminase affects the duration and intensity of deep sleep in humans. Proc Natl Acad Sci U S A 102: 15676–15681.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Perras B, Pannenborg H, Marshall L, et al, 1999 Beneficial treatment of age-related sleep disturbances with prolonged intranasal vasopressin. J Clin Psychopharmacol 19: 28–36.PubMedCrossRefGoogle Scholar
  81. 81.
    van West D, Del-Favero J, Aulchenko Y, et al, 2004 A major SNP haplotype of the arginine vasopressin 1B receptor protects against recurrent major depression. Mol Psychiatry 9: 287–292.PubMedCrossRefGoogle Scholar
  82. 82.
    Abdelfatah D, Shaker H, Ismail M, et al, 2009 Nocturnal polyuria and nocturnal arginine vasopressin (AVP): A key factor in the pathophysiology of monosymptomatic nocturnal enuresis. Neurourol Urodyn 28: 506–509.PubMedCrossRefGoogle Scholar
  83. 83.
    Gozmen S, Keskin S, Akil I, 2008 Enuresis nocturna and sleep quality. Pediatr Nephrol 23: 1293–1296.PubMedCrossRefGoogle Scholar
  84. 84.
    Schneider T, de la Rosette JJ, Michel MC, 2009 Nocturia: a non-specific but important symptom of urological disease. Int J Urol 16: 249–256.PubMedCrossRefGoogle Scholar
  85. 85.
    Antonijevic IA, Murck H, Bohlhalter S, et al, 2000 NPY promotes sleep and inhibits ACTH and cortisol release in young men. Neuropharmacol 39: 1474–1481.CrossRefGoogle Scholar
  86. 86.
    Held K, Antonijevic I, Murck H, Kuenzel H, Steiger A, 2006 Neuropeptide Y (NPY) shortens sleep latency but does not suppress ACTH and cortisol in depressed patients and normal controls. Psychoneuroendocrinol 31: 100–107.CrossRefGoogle Scholar
  87. 87.
    Drucker-Colin R, Bernal-Pedraza J, Fernandez-Cancino F, et al, 1984 Is vasoactive intestinal polypeptide (VIP) a sleep factor? [Abstract]. Peptid 5: 837–840.CrossRefGoogle Scholar
  88. 88.
    Murck H, Guldner J, Colla-Miiller M, et al, 1996 VIP decelerates non-REM-REM cycles and modulates hormone secretion during sleep in men. Am J Physiol 271: R905–R911.PubMedCrossRefGoogle Scholar
  89. 89.
    Roky R, Obál F Jr, Valatx JL, et al, 1995 Prolactin and rapid eye movement sleep regulation. Sleep 18: 536–542.PubMedGoogle Scholar
  90. 90.
    Frieboes RM, Murck H, Stalla GK, Antonijevic IA, Steiger A, 1998 Enhanced slow wave sleep in patients with prolactinoma. J Clin Endocrinol Metab 83: 2706–2710.PubMedCrossRefGoogle Scholar
  91. 91.
    Antonijevic IA, Murck H, Frieboes RM, Uhr M, Steiger A, 2003 On the role of menopause for sleep-endocrine alterations associated with major depression. PNEC 28: 401–418.Google Scholar
  92. 92.
    Wiklund I, Karlberg J, Mattsson L-A, 1993 Quality of life of post-menopausal women on a regimen of transdermal estradiol therapy: a double-blind placebo-controlled study [Abstract]. Am J Obstet Gynecol 168: 824–830.PubMedCrossRefGoogle Scholar
  93. 93.
    Polo-Kantola P, Erkkola R, Helenius H, Irjala K, Polo O, 1998 When does estrogen replacement therapy improve sleep quality? Am J Obstet Gynecol 178: 1002–1009.PubMedCrossRefGoogle Scholar
  94. 94.
    Shin K, Shapiro C, 2003 Menopause, sex hormones, and sleep. Bibolar Disord 5: 106–109.CrossRefGoogle Scholar
  95. 95.
    Antonijevic IA, Stalla GK, Steiger A, 2000 Modulation of the sleep electroencephalogram by estrogen replacement in postmenopausal women. Am J Obstet Gynecol 182: 277–282.PubMedCrossRefGoogle Scholar
  96. 96.
    Malacara JM, Pérez-Luque EL, Martínez-Garza S, et al, 2004 The relationship of estrogen receptor-alpha polymorphism with symptoms and other characteristics in post-menopausal women. Maturitas 49:163–169.PubMedCrossRefGoogle Scholar
  97. 97.
    Viswanathan AN, Schernhammer ES, 2009 Circulating melatonin and the risk of breast and endometrial cancer in women. Cancer Lett 281: 1–7.PubMedCrossRefGoogle Scholar
  98. 98.
    Natale V, Albertazzi P, Zini M, Di Marco R, 2001 Exploration of cyclical changes in memory and mood in postmenopausal women taking sequential combined oestrogen and progestogen preparations. Br J Obstet Gynaecol 108: 286–290.Google Scholar
  99. 99.
    Montplaisir J, Lorrain J, Denesle R, Petit D, 2001 Sleep in menopause. differential effects of two forms of hormone replacement therapy. Menopause 8: 10–16.PubMedCrossRefGoogle Scholar
  100. 100.
    Kalleinen N, Polo O, Himanen SL, Joutsen A, Polo-Kantola P, 2008 The effect of estrogen plus progestin treatment on sleep: a randomized, placebo-controlled, double-blind trial in premenopausal and late postmenopausal women. Climacteric 11: 233–243.PubMedCrossRefGoogle Scholar
  101. 101.
    Friess E, Trachsel L, Guldner J, et al, 1995 DHEA administration increases rapid eye movement sleep and EEG power in the sigma frequency range. Am J Physiol 268: E107–E113.PubMedGoogle Scholar
  102. 102.
    Schiffelholz T, Holsboer F, Lancel M, 2000 High doses of systemic DHEA-sulfate do not affect sleep structure and elicit moderate changes in non-REM sleep. Physiol Behav 69: 399–404.PubMedCrossRefGoogle Scholar
  103. 103.
    Dayal M, Sammel MD, Zhao J, et al, 2005 Supplementation with DHEA: effect on muscle size, strength, quality of life, and lipids [Abstract]. J Womens Health (Larchmt) 14: 391–400.CrossRefGoogle Scholar
  104. 104.
    Nikolakopoulou D, Stamatakis A, 2009 The Role of Melatonin in the Pathology of the Cardiovascular System. Nosileftiki, 48: 143–149.Google Scholar
  105. 105.
    Cajochen C, Kräuchi K, Wirz-Justice A, 2003 Role of melatonin in the regulation of human circadian rhythms and sleep. J Neuroendocrinol 15: 432–437.PubMedCrossRefGoogle Scholar
  106. 106.
    Zeitzer JM, Ayas NT, Shea SA, Brown R, Czeisler CA, 2000 Absence of detectable melatonin and preservation of cortisol and thyrotropin rhythms in tetraplegia. J Clin Endocrinol Metab 85: 2189–2196.PubMedGoogle Scholar
  107. 107.
    Youngstedt SD, Kripke DF, Elliott JA, 1998 Melatonin excretion is not related to sleep in the elderly. J Pineal Res 24: 142–145.PubMedCrossRefGoogle Scholar
  108. 108.
    Hughes RJ, Sack RL, Lewy AJ, 1998 The role of melatonin and circadian phase in age-related sleep-maintenance insomnia: assessment in a clinical trial of melatonin replacement. Sleep 21: 52–68.PubMedGoogle Scholar
  109. 109.
    Zhdanova IV, Wurtman RJ, Morabito C, Piotrovska VR, Lynch HJ, 1996 Effects of low oral doses of melatonin, given 2-4 hours before habitual bedtime, on sleep in normal young humans. Sleep 19: 423–431.PubMedCrossRefGoogle Scholar
  110. 110.
    Zhdanova IV, 2005. Melatonin as a hypnotic: Pro. Sleep Med Rev 9: 51–65.PubMedCrossRefGoogle Scholar
  111. 111.
    Van den Heuvel CJ, Ferguson SA, Mila Macchi M, Dawson D, 2005 Melatonin as a hypnotic: Con. Sleep Med Rev 9: 71–80.PubMedCrossRefGoogle Scholar
  112. 112.
    Gehrman PR, Connor DJ, Martin JL, et al, 2009 Mela-tonin fails to improve sleep or agitation in double-blind randomized placebo-controlled trial of institutionalized patients with Alzheimer disease. Am J Geriatr Psychiatry 17: 166–169.PubMedPubMedCentralCrossRefGoogle Scholar
  113. 113.
    Srinivasan V, Pandi-Perumal SR, Cardinali DP, et al, 2006 Melatonin in Alzheimer’s disease and other neu-rodegenerative disorders. Behav Brain Funct 2: 15.PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Gehrman PR, Connor DJ, Martin JL, et al, 2009 Melatonin fails to improve sleep or agitation in double-blind randomized placebo-controlled trial of institutionalized patients with Alzheimer disease. Am J Geriatr Psychiatry 17: 166–169.PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Braam W, Smits MG, Didden R, et al, 2009 Exogenous melatonin for sleep problems in individuals with intellectual disability: a meta-analysis. Dev Med Child Neurol 51: 340–349.PubMedCrossRefGoogle Scholar
  116. 116.
    Srinivasan V, Spence DW, Pandi-Perumal SR, et al, 2008 Therapeutic actions of melatonin in cancer: possible mechanisms. Integr Cancer Ther 7: 189–203.PubMedCrossRefGoogle Scholar
  117. 117.
    Lyssenko V, Nagorny CL, Erdos MR, et al, 2009 Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion. Nat Genet 41: 82–88.PubMedPubMedCentralCrossRefGoogle Scholar
  118. 118.
    Bouatia-Naji N, Bonnefond A, Cavalcanti-Proença C, et al, 2009 A variant near MTNR1B is associated with increased fasting plasma glucose levels and type 2 diabetes risk. Nat Genet 41: 89–94.CrossRefGoogle Scholar
  119. 119.
    Prokopenko I, Langenberg C, Florez JC, et al, 2009 Variants in MTNR1B influence fasting glucose levels. Nat Genet 41: 77–81.CrossRefGoogle Scholar
  120. 120.
    Wade A, Downie S, 2008 Prolonged-release melatonin for the treatment of insomnia in patients over 55 years. Expert Opin Investig Drugs 17: 1567–1572.PubMedCrossRefGoogle Scholar
  121. 121.
    Rivara S, Mor M, Bedini A, Spadoni G, Tarzia G, 2008 Melatonin receptor agonists: SAR and applications to the treatment of sleep-wake disorders. Curr Top Med Chem 8: 954–968.PubMedCrossRefGoogle Scholar
  122. 122.
    Simpson D, Curran MP, 2008 Ramelteon: a review of its use in insomnia. Drugs 68: 1901–1919.PubMedCrossRefGoogle Scholar
  123. 123.
    Gross PK, Nourse R, Wasser TE, 2009 Ramelteon for insomnia symptoms in a community sample of adults with generalized anxiety disorder: an open label study. J Clin Sleep Med 5: 28–33.PubMedPubMedCentralGoogle Scholar
  124. 124.
    Dobkin RD, Menza M, Bienfait KL, et al, 2009 Ramelteon for the treatment of insomnia in menopausal women. Menopause Int 15: 13–18.PubMedPubMedCentralCrossRefGoogle Scholar
  125. 125.
    Srinivasan V, Pandi-Perumal SR, Trakht I, et al, 2009 Pathophysiology of depression: role of sleep and the melatonergic system. Psychiatry Res 165: 201–214.PubMedCrossRefGoogle Scholar
  126. 126.
    Nishino S, Arrigoni J, Shelton J, et al, 1997 Effects of thyrotropin-releasing hormone and its analogs on daytime sleepiness and cataplexy in canine narcolepsy. J Neurosci 17: 6401–6408.PubMedCrossRefGoogle Scholar
  127. 127.
    Hemmeter U, Rothe B, Guldner J, Holsboer F, Steiger A, 1998 Effects of thyrotropin-releasing hormone on the sleep EEG and nocturnal hormone secretion in male volunteers. Neuropsychobiol 38: 25–31.CrossRefGoogle Scholar
  128. 128.
    Staner L, Duval F, Haba J, et al, 2003 Disturbances in hypothalamo pituitary adrenal and thyroid axis identify different sleep EEG patterns in major depressed patients. J Psychiatr Res 37: 1–8.PubMedCrossRefGoogle Scholar
  129. 129.
    Staner L, Duval F, Calvi-Gries F, et al, 2001 Morning and evening TSH response to TRH and sleep EEG disturbances in major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry 25: 535–547.PubMedCrossRefGoogle Scholar
  130. 130.
    Nishino S, Ripley B, Overeem S, et al, 2000 Hypocretin (orexin) deficiency in human narcolepsy. Lancet 355: 39–40.PubMedCrossRefGoogle Scholar
  131. 131.
    Taylor MM, Samson WK, 2003 The other side of the orexins: endocrine and metabolic actions. Am J Physiol Endocrinol Metab 284: E13–E17.PubMedCrossRefGoogle Scholar
  132. 132.
    Nishino S, 2003 The Hypocretin/Orexin System in Health and Disease. Biol Psychiatry 54: 87–95.PubMedCrossRefGoogle Scholar
  133. 133.
    Nishino S, Yoshida Y, 2003 History and perspectives of hypocretin/orexin research in sleep medicine. Sleep Biol Rhyth 1: 43–54.CrossRefGoogle Scholar
  134. 134.
    Watson CJ, Soto-Calderon H, Lydic R, Baghdoyan HA, 2008 Pontine reticular formation (PnO) administration of hypocretin-1 increases PnO GABA levels and wake-fulness. Sleep 31: 453–464.PubMedPubMedCentralCrossRefGoogle Scholar
  135. 135.
    Nishino S, 2007. The hypocretin/orexin receptor: therapeutic prospective in sleep disorders. Expert Opin Investig Drugs 16: 1785–1797.Google Scholar
  136. 136.
    Saper CB, Chou TC, Scammell TE, 2001 The sleep switch: hypothalamic control of sleep and wakefulness. Trends Neurosci 24: 726–731.PubMedCrossRefGoogle Scholar
  137. 137.
    Klein J, Sato A, 2000 The HLA system. Second of two parts. N Engl J Med 343: 782–786.PubMedCrossRefGoogle Scholar
  138. 138.
    Hallmayer J, Faraco J, Lin L, et al, 2009 Narcolepsy is strongly associated with the T-cell receptor alpha locus. Nat Genet 41: 708–711.PubMedPubMedCentralCrossRefGoogle Scholar
  139. 139.
    “Narcolepsy is an autoimmune disorder, Stanford researcher says”. EurekAlert. American Association for the Advancement of Science. 2009-05-03. Retrieved on 2009-07-12.Google Scholar
  140. 140.
    Nishino S, Sakurai E, Nevsimalova S, et al, 2009 Decreased CSF histamine in narcolepsy with and without low CSF hypocretin-1 in comparison to healthy controls. Sleep 32: 175–180.PubMedPubMedCentralCrossRefGoogle Scholar
  141. 141.
    Nishino S, Okuro M, Kotorii N, et al, 2009 Hypocretin/orexin and narcolepsy new basic and clinical insights. Acta Physiol (Oxf) Jun 25. [Epub ahead of print]Google Scholar
  142. 142.
    Knudsen S, Jennum PJ, Korsholm K, et al, 2008 Normal levels of cerebrospinal fluid hypocretin-1 and daytime sleepiness during attacks of relapsing-remitting multiple sclerosis and monosymptomatic optic neuritis. Mult Scler 14: 734–738.PubMedCrossRefGoogle Scholar
  143. 143.
    Aksu K, Firat Güven S, Aksu F, et al, 2009 Obstructive sleep apnoea, cigarette smoking and plasma orexin—A in a sleep clinic cohort. J Int Med Res 37: 331–340.PubMedCrossRefGoogle Scholar
  144. 144.
    Asai H, Hirano M, Furiya Y, et al, 2009 Cerebrospinal fluid-orexin levels and sleep attacks in four patients with Parkinson’s disease. Clin Neurol Neurosurg 111: 341–344.PubMedCrossRefGoogle Scholar
  145. 145.
    Poceta JS, Parsons L, Engelland S, et al, 2009 Circadian rhythm of CSF monoamines and hypocretin-1 in restless legs syndrome and Parkinson’s disease. Sleep Med 10: 129–133.PubMedCrossRefGoogle Scholar
  146. 146.
    Rissling I, Körner Y, Geller F, et al, 2005 Preprohypocretin polymorphisms in Parkinson disease patients reporting “sleep attacks”. Sleep 28: 871–875.PubMedCrossRefGoogle Scholar
  147. 147.
    Cortese S, Konofal E, Lecendreux M, 2008 Alertness and feeding behaviors in ADHD: does the hypocretin/orexin system play a role? Med Hypotheses 71: 770–775.PubMedCrossRefGoogle Scholar
  148. 148.
    Baranowska B, Baranowska-Bik A, Bik W, et al, 2008 The role of leptin and orexins in the dysfunction of hypothalamo-pituitary-gonadal regulation and in the mechanism of hyperactivity in patients with anorexia nervosa. Neuro Endocrinol Lett 29: 37–40.PubMedGoogle Scholar
  149. 149.
    Knutson KL, Van Cauter E, 2008 Associations between sleep loss and increased risk of obesity and diabetes. Ann N Y Acad Sci 1129: 287–304.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Hellenic Endocrine Society 2009

Authors and Affiliations

  • Grigorios Kotronoulas
    • 1
    Email author
  • Antonios Stamatakis
    • 2
  • Fotini Stylianopoulou
    • 2
  1. 1.Cancer Care Research Centre (CCRC)University of StirlingStirlingScotland, UK
  2. 2.Laboratory of Biology-Biochemistry, Faculty of NursingUniversity of AthensAthensGreece

Personalised recommendations