Advertisement

Neuroendocrine Role of the Orexins (Hypocretins)

  • Shahrad Taheri
Part of the Contemporary Clinical Neuroscience book series (CCNE)

Abstract

Although the orexin (hypocretin) neuron cell bodies are exclusively located in the lateral perifornical hypothalamus (the classical “feeding center”), they send projections throughout the neuraxis (1,2). This suggests that orexin neuropeptides and their receptors have functions beyond their originally observed effects on food intake and their currently accepted pivotal role in the regulation of sleep and wakefulness (3, 4, 5, 6). In particular, orexin fibers have been observed to innervate several brain, and specifically hypothalamic, regions that are intimately involved in the regulation of pituitary hormone secretion. Therefore, a link between the orexins and pituitary hormone secretion appeared highly likely from the outset. This view was underscored by the observed role of orexins in sleep regulation, since the secretion of some hormones is closely linked to circadian rhythms (e.g., corticotrophin, [AC TH]) and sleep (e.g., growth hormone).

Keywords

Prolactin Secretion Pituitary Hormone Secretion Hypothalamic Explants Orexin Fiber Neuroendocrine Role 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Peyron, C., Tighe, D.K., van den Pol, A.N. et al. (1998) Neurons containing hypocretin (orexin) project to multiple neuronal systems. J. Neurosci. 18, 9996–10015.PubMedGoogle Scholar
  2. 2.
    Taheri, S., Zeitzer, J.M., Mignot, E. (2002) The role of hypocretins (orexins) in sleep regulation and narcolepsy. Annu. Rev. Neurosci. 25, 283–313.PubMedCrossRefGoogle Scholar
  3. 3.
    Sakurai, T., Amemiya, A., Ishii, M. et al. (1998) Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 92, 573–585.PubMedCrossRefGoogle Scholar
  4. 4.
    Taheri, S., Bloom, S. (2001) Orexins/hypocretins: waking up the scientific world. Clin. Endocrinol. (Oxf). 54, 421–429.CrossRefGoogle Scholar
  5. 5.
    Willie, J.T., Chemelli, R.M., Sinton, C.M., and Yanagisawa M. (2001) To eat or to sleep? Orexin in the regulation of feeding and wakefulness. Annu. Rev. Neurosci. 24, 429–458.PubMedCrossRefGoogle Scholar
  6. 6.
    Sakurai, T. (2002) Roles of orexins in the regulation of feeding and arousal. Sleep Med. 3(suppl. 2), S3–S9.PubMedCrossRefGoogle Scholar
  7. 7.
    Jennes, L. and Conn, P.M. (1994) Gonadotropin-releasing hormone and its receptors in rat brain. Front. Neuroendocrinol. 15, 51–77.PubMedCrossRefGoogle Scholar
  8. 8.
    Taheri, S., Mahmoodi, M., Opacka-Juffry, J., Ghatei, M.A., and Bloom, S.R. (1999) Distribution and quantification of immunoreactive orexin A in rat tissues. FEBS Lett. 457, 157–161.PubMedCrossRefGoogle Scholar
  9. 9.
    Pu, S., Jain, M.R., Kalra, P.S., and Kalra, S.P. (1998) Orexins, a novel family of hypothalamic neuropeptides, modulate pituitary luteinizing hormone secretion in an ovarian steroid-dependent manner. Regul. Pept. 78, 133–136.PubMedCrossRefGoogle Scholar
  10. 10.
    Irahara, M., Tamura, T., Matuzaki, T., et al. (2001) Orexin-A suppresses the pulsatile secretion of luteinizing hormone via beta-endorphin. Biochem. Biophys. Res. Commun. 281, 232–236.PubMedCrossRefGoogle Scholar
  11. 11.
    Kohsaka, A., Watanobe, H., Kakizaki, Y., Suda, T., and Schioth, H.B. (2001) A significant participation of orexin-A, a potent orexigenic peptide, in the preovulatory luteinizing hormone and prolactin surges in the rat. Brain Res. 898, 166–170.PubMedCrossRefGoogle Scholar
  12. 12.
    Russell, S.H., Small, C.J., Kennedy, A.R., et al. (2001) Orexin A interactions in the hypothalamopituitary gonadal axis. Endocrinology 142, 5294–5302.PubMedCrossRefGoogle Scholar
  13. 13.
    Mahesh, V.B. and Brann, D.W. (1998) Regulation of the preovulatory gonadotropin surge by endogenous steroids. Steroids 63, 616–629.PubMedCrossRefGoogle Scholar
  14. 14.
    Hagan, J.J., Leslie, R.A., Patel, S., et al. (1999) Orexin A activates locus coeruleus cell firing and increases arousal in the rat. Proc. Natl. Acad. Sci. U S A 96, 10911–10916.PubMedCrossRefGoogle Scholar
  15. 15.
    Russell, S.H., Kim, M.S., Small, C.J., et al. (2000) Central administration of orexin A suppresses basal and domperidone stimulated plasma prolactin. J. Neuroendocrinol. 12, 1213–1218.PubMedCrossRefGoogle Scholar
  16. 16.
    Jones, D.N., Gartlon, J., Parker, F., et al. (2001) Effects of centrally administered orexin-B and orexin-A: a role for orexin-1 receptors in orexin-B-induced hyperactivity. Psychopharmacology (Berl.) 153, 210–218.CrossRefGoogle Scholar
  17. 17.
    Freeman, M.E., Kanyicska, B., Lerant, A., and Nagy, G. (2000) Prolactin: structure, function, and regulation of secretion. Physiol. Rev. 80, 1523–1631.PubMedGoogle Scholar
  18. 18.
    Hsueh, Y.C., Cheng, S.M., Pan, J.T. (2002) Fasting stimulates tuberoinfundibular dopaminergic neuronal activity and inhibits prolactin secretion in oestrogen-primed ovariectomized rats: involvement of orexin A and neuropeptide Y. J. Neuroendocrinol. 14, 745–752.PubMedCrossRefGoogle Scholar
  19. 19.
    Lux-Lantos, V., Becu-Villalobos, D., Bianchi, M. et al. (2001) GABA(B) receptors in anterior pituitary cells. Mechanism of action coupled to endocrine effects. Neuroendocrinology 73, 334–343.PubMedCrossRefGoogle Scholar
  20. 20.
    Malabu, U.H., Kilpatrick, A., Ware, M., Vernon, R.G., and Williams, G. (1994) Increased neuropeptide Y concentrations in specific hypothalamic regions of lactating rats: possible relationship to hyperphagia and adaptive changes in energy balance. Peptides 15, 83–87.PubMedCrossRefGoogle Scholar
  21. 21.
    Pickavance, L., Dryden, S., Hopkins, D., et al. (1996) Relationships between hypothalamic neuropeptide Y and food intake in the lactating rat. Peptides 17, 577–582.PubMedCrossRefGoogle Scholar
  22. 22.
    Brogan, R.S., Mitchell, S.E., Trayhurn, P., and Smith, M.S. (1999) Suppression of leptin during lactation: contribution of the suckling stimulus versus milk production. Endocrinology 140, 2621–2627.PubMedCrossRefGoogle Scholar
  23. 23.
    Smith, M.S. and Grove, K.L. (2002) Integration of the regulation of reproductive function and energy balance: lactation as a model. Front. Neuroendocrinol. 23, 225–256.PubMedCrossRefGoogle Scholar
  24. 24.
    Cai, X.J., Denis, R., Vernon, R.G., et al. (2001) Food restriction selectively increases hypothalamic orexin-B levels in lactating rats. Regul. Pept. 97, 163–168.PubMedCrossRefGoogle Scholar
  25. 25.
    Kok, S.W., Roelfsema, F., Overeem, S., et al. (2004) Pulsatile LH release is diminished, while FSH secretion is normal in hypocretin deficient narcoleptic men. Am. J. Physiol. Endocrinol. Metab. 287, E630–E636.PubMedCrossRefGoogle Scholar
  26. 26.
    Mitsuma, T., Hirooka, Y., Mori, Y., et al. (1999) Effects of orexin A on thyrotropin-releasing hormone and thyrotropin secretion in rats. Horm. Metab. Res. 31, 606–609.PubMedCrossRefGoogle Scholar
  27. 27.
    Russell, S.H., Small, C.J., Dakin, C.L., et al. (2001) The central effects of orexin-A in the hypothalamic-pituitary-adrenal axis in vivo and in vitro in male rats. J. Neuroendocrinol 13, 561–566.PubMedCrossRefGoogle Scholar
  28. 28.
    Russell, S.H., Small, C.J., Sunter, D., et al. (2002) Chronic intraparaventricular nuclear administration of orexin A in male rats does not alter thyroid axis or uncoupling protein-1 in brown adipose tissue. Regul. Pept. 104, 61–68.PubMedCrossRefGoogle Scholar
  29. 29.
    Yoshida, Y., Fujiki, N., Maki, R.A., Schwarz, D., and Nishino, S. (2003) Differential kinetics of hypocretins in the cerebrospinal fluid after intracerebroventricular administration in rats. Neurosci. Lett. 346, 182–186.PubMedCrossRefGoogle Scholar
  30. 30.
    Marcus, J.N., Aschkenasi, C.J., Lee, C.E., et al. (2001) Differential expression of orexin receptors 1 and 2 in the rat brain. J. Comp. Neurol. 435, 6–25.PubMedCrossRefGoogle Scholar
  31. 31.
    Lopez, M., Seoane, L., Senaris, R.M., and Dieguez, C. (2001) Prepro-orexin mRNA levels in the rat hypothalamus, and orexin receptors mRNA levels in the rat hypothalamus and adrenal gland are not influenced by the thyroid status. Neurosci. Lett. 300, 171–175.PubMedCrossRefGoogle Scholar
  32. 32.
    Emlen, W., Segal, D.S., and Mandell, A.J. (1972) Thyroid state: effects on pre-and postsynaptic central noradrenergic mechanisms. Science 175, 79–82.PubMedCrossRefGoogle Scholar
  33. 33.
    Yamamoto, T. Hirose, N., and Miyoshi, K. (1977) Polygraphic study of periodic breathing and hypersomnolence in a patient with severe hypothyroidism. Eur. Neurol. 15, 188–193.PubMedGoogle Scholar
  34. 34.
    Carpenter, A.C. and Timiras, P.S. (1982) Sleep organization in hypo-and hyperthyroid rats. Neuroendocrinology 34, 438–443.PubMedGoogle Scholar
  35. 35.
    Mignot, E., Lammers, G.J., Ripley, B., et al. (2002) The role of cerebrospinal fluid hypocretin measurement in the diagnosis of narcolepsy and other hypersomnias. Arch. Neurol. 59, 1553–1562.PubMedCrossRefGoogle Scholar
  36. 36.
    Jessop, D.S. (1999) Stimulatory and inhibitory regulators of the hypothalamo-pituitaryadrenocortical axis. Baillieres Best Pract. Res. Clin. Endocrinol. Metab. 13, 491–501.PubMedCrossRefGoogle Scholar
  37. 37.
    Backberg, M., Hervieu, G., Wilson, S., and Meister, B. (2002) Orexin receptor-1 (OX-R1) immunoreactivity in chemically identified neurons of the hypothalamus: focus on orexin targets involved in control of food and water intake. Eur. J. Neurosci. 15, 315–328.PubMedCrossRefGoogle Scholar
  38. 38.
    Jaszberenyi, M., Bujdoso, E., Pataki, I., and Telegdy, G. (2000) Effects of orexins on the hypothalamicpituitary-adrenal system. J. Neuroendocrinol. 12, 1174–1178.PubMedCrossRefGoogle Scholar
  39. 39.
    Jaszberenyi, M., Bujdoso, E., and Telegdy, G. (2001) The role of neuropeptide Y in orexin-induced hypothalamic-pituitary-adrenal activation. J. Neuroendocrinol. 13, 438–441.PubMedCrossRefGoogle Scholar
  40. 40.
    Al-Barazanji, K.A., Wilson, S., Baker, J., Jessop, D.S., and Harbuz, M.S. (2001) Central orexin-A activates hypothalamic-pituitary-adrenal axis and stimulates hypothalamic corticotropin releasing factor and arginine vasopressin neurones in conscious rats. J. Neuroendocrinol. 13, 421–424.PubMedCrossRefGoogle Scholar
  41. 41.
    Kuru, M., Ueta, Y., Serino, R., et al. (2000) Centrally administered orexin/hypocretin activates HPA axis in rats. Neuroreport 11, 1977–1980.PubMedCrossRefGoogle Scholar
  42. 42.
    Samson, W.K., Taylor, M.M., Follwell, M., and Ferguson, A.V. (2002) Orexin actions in hypothalamic paraventricular nucleus: physiological consequences and cellular correlates. Regul. Pept. 104, 97–103.PubMedCrossRefGoogle Scholar
  43. 43.
    Ida, T., Nakahara, K., Kuroiwa, T., et al. (2000) Both corticotropin releasing factor and neuropeptide Y are involved in the effect of orexin on the food intake in rats. Neurosci. Lett. 293, 119–122.PubMedCrossRefGoogle Scholar
  44. 44.
    Ida, T., Nakahara, K., Murakami, T., Hanada, R., Nakazato, M., and Murakami, N. (2000) Possible involvement of orexin in the stress reaction in rats. Biochem. Biophys. Res. Commun. 270, 318–323.PubMedCrossRefGoogle Scholar
  45. 45.
    Zhu, L., Onaka, T., Sakurai, T., and Yada, T. (2002) Activation of orexin neurones after noxious but not conditioned fear stimuli in rats. Neuroreport 13, 1351–1353.PubMedCrossRefGoogle Scholar
  46. 46.
    Zeitzer, J.M., Buckmaster, C.L., Parker, K.J., Hauck, C.M., Lyons, D.M., and Mignot, E. (2003) Circadian and homeostatic regulation of hypocretin in a primate model: implications for the consolidation of wakefulness. J. Neurosci. 23, 3555–3560.PubMedGoogle Scholar
  47. 47.
    Nishino, S., Ripley, B., Overeem, S., Lammers, G.J., and Mignot, E. (2000) Hypocretin (orexin) deficiency in human narcolepsy. Lancet 355, 39–40.PubMedCrossRefGoogle Scholar
  48. 48.
    Mignot, E., Taheri, S., and Nishino, S. (2002) Sleeping with the hypothalamus: emerging therapeutic targets for sleep disorders. Nat. Neurosci. 5(suppl.), 1071–1075.PubMedCrossRefGoogle Scholar
  49. 49.
    Higuchi, T., Takahashi, Y., Takahashi, K., Niimi, Y., and Miyasita, A. (1979) Twenty-four-hour secretory patterns of growth hormone, prolactin, and cortisol in narcolepsy. J. Clin. Endocrinol. Metab. 49, 197–204.PubMedCrossRefGoogle Scholar
  50. 50.
    Kok, S.W., Roelfsema, F., Overeem, S., et al. (2002) Dynamics of the pituitary-adrenal ensemble in hypocretin-deficient narcoleptic humans: blunted basal adrenocorticotropin release and evidence for normal time-keeping by the master pacemaker. J. Clin. Endocrinol. Metab. 87, 5085–5091.PubMedCrossRefGoogle Scholar
  51. 51.
    Stricker-Krongrad, A. and Beck, B. (2002) Modulation of hypothalamic hypocretin/orexin mRNA expression by glucocorticoids. Biochem. Biophys. Res. Commun. 296, 129–133.PubMedCrossRefGoogle Scholar
  52. 52.
    Lopez, M., Seoane, L.M., Tovar, S., Nogueiras, R., Dieguez, C., and Senaris, R. (2004) Orexin-A regulates growth hormone-releasing hormone mRNA content in a nucleus-specific manner and somatostatin mRNA content in a growth hormone-dependent fashion in the rat hypothalamus. Eur. J. Neurosci. 19, 2080–2088.PubMedCrossRefGoogle Scholar
  53. 53.
    Clark, R.W., Schmidt, H.S., and Malarkey, W.B. (1979) Disordered growth hormone and prolactin secretion in primary disorders of sleep. Neurology 29, 855–861.PubMedGoogle Scholar
  54. 54.
    Overeem, S., Kok, S.W., Lammers, G.J., et al. (2003) Somatotropic axis in hypocretin-deficient narcoleptic humans: altered circadian distribution of GH-secretory events. Am. J. Physiol. Endocrinol. Metab. 284, E641–E647.PubMedGoogle Scholar
  55. 55.
    Willie, J.T., Sakurai, T., Hara, J., Takahira, H., Gershenfeld, H.K., and Yanagisawa, M. (2002) Ectopic expression of orexin transgene alters body weight and energy metabolism in mice. Society for Neuroscience Meeting, Orlando, FL, abstract 320.8.Google Scholar
  56. 56.
    Date, Y., Mondal, M.S., Matsukura, S., et al. (2000) Distribution of orexin/hypocretin in the rat median eminence and pituitary. Brain Res. Mol. Brain Res. 76, 1–6.PubMedCrossRefGoogle Scholar
  57. 57.
    Blanco, M., Lopez, M., Garcia-Caballero, T., et al. (2001) Cellular localization of orexin receptors in human pituitary. J. Clin. Endocrinol. Metab. 86, 1616–1619.CrossRefGoogle Scholar
  58. 58.
    Samson, W.K. and Taylor, M.M. (2001) Hypocretin/orexin suppresses corticotroph responsiveness in vitro. Am. J. Physiol. Regul. Integr. Comp. Physiol. 281, R1140–R1145.PubMedGoogle Scholar

Copyright information

© Humana Press Inc., Totowa, NJ 2006

Authors and Affiliations

  • Shahrad Taheri
    • 1
  1. 1.Henry Wellcome Laboratories for Integrative Neuroscience and EndocrinologyUniversity of BristolUK

Personalised recommendations