Neuroendocrinology and Brain Peptides An Emerging New Frontier in Neurobiology

An Emerging New Frontier in Neurobiology
  • Joseph B. Martin


This chapter will describe recent advances in the field of neuroendocrinology and brain peptides. First, principles of neurosecretion, including the processes of peptide hormone biosynthesis, are considered. Then, two examples of hy-pothalamic-pituitary regulatory systems, those for prolactin and ACTH, are examined because they illustrate principles of neuroendocrine control. Last, the emerging field of brain peptides is reviewed. It is apparent that peptide substances, which include the hormones of the hypothalamus and pituitary, are of great importance for an understanding of brain function.


Vasoactive Intestinal Polypeptide Thyrotropin Release Hormone Median Eminence Prolactin Secretion ACTH Secretion 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Akil, H., Richardson, D. E., Barchas, J. D., and Li, C. H., 1978, Appearance of β-endorphin-like immunoreactivity in human ventricular cerebrospinal fluid upon analgesic electrical stimulation, Proc. Natl. Acad. Sci. USA 75:5170.PubMedCrossRefGoogle Scholar
  2. Aronin, N., Cooper, P E., Lorenz, L. J., Bird, E. D., Sagar, S. M., Leeman, S. E., and Martin, J. B., 1983, Somatostatin is increased in the basal ganglia in Huntington’s disease, Ann. Neurol. 13:519.PubMedCrossRefGoogle Scholar
  3. Basbaum, A. I., and Fields, H. L., 1978, Endogenous pain control mechanisms: Review and hypothesis, Ann. Neurol. 4:451.PubMedCrossRefGoogle Scholar
  4. Bird, E. D., 1980, Chemical pathology of Huntington’s disease, Annu. Rev. Pharmacol. Toxicol. 20:533.PubMedCrossRefGoogle Scholar
  5. Brown, M. R., Rivier, J. E., Kobayashi, R., and Vale, W. W., 1978, Neurotensin-like and bombesin-like peptides: CNS distribution and actions, in: Gut Hormones (S. R. Bloom, ed.), pp. 550–558, Churchill Livingston, Edinburgh.Google Scholar
  6. Brown, M. R., Tache, Y., Rivier, J., and Pittman, Q., 1981, Peptides and regulation of body temperature in: Neurosecretion and Brain Peptides: Implication for Brain Function and Neurological Disease (J. B. Martin, S. Reichlin, and K. L. Bick, eds.), pp. 397–408, Raven Press, New York.Google Scholar
  7. Comb, M., Seeburg, P. H., Adelman, J., Eiden, L., and Herbert, E., 1982, Primary structure of the human Met- and Leu-enkephalin precursor and its mRNA, Nature (London) 295:663.CrossRefGoogle Scholar
  8. Cooper, K. E., Kasting, N. W., Lederis, K., and Veale, W. L., 1979, Evidence supporting a role for endogenous vasopressin in natural suppression of fever in the sheep, J. Physiol. 295:33.PubMedGoogle Scholar
  9. Davies, P., Katzman, R., and Terry, R. D., 1980, Reduced somatostatin-like immunoreactivity in cerebral cortex from cases of Alzheimer disease and Alzheimer senile dementia, Nature (London) 288:279.CrossRefGoogle Scholar
  10. de Kloet, R., and de Weid, D., 1980, The brain as target tissue for hormones of pituitary origin: Behavioral and biochemical studies, in: Frontiers in Neuroendocrinology, Vol. 6 (L. Martini and W. F. Ganong, eds.), pp. 157–201, Raven Press, New York.Google Scholar
  11. Dockray, G. J., 1979, Evolutionary relationships of the gut hormones, Fed. Proc. 38:2295.PubMedGoogle Scholar
  12. Dogterom, J., van Wimersma Griedanus, T. B., and Swaab, D. F., 1977, Evidence for the release of vasopressin and oxytocin into cerebrospinal fluid: Measurements in plasma and CSF of intact and hypophysectomized rats, Neuroendocrinology 24:108.PubMedCrossRefGoogle Scholar
  13. Emson, P. C., Fahrenkrug, J., and Spokes, E. G. S., 1979, Vasoactive intestinal polypeptide (VIP): Distribution in normal human brain and in Huntington’s disease, Brain Res. 173:174.PubMedCrossRefGoogle Scholar
  14. Emson, P. C., Arregui, A., Clement-Jones, V., Sandberg, B. E. B., and Rossor, M., 1980, Regional distribution of methionine-enkephalin and substance P-like immunoreactivity in normal human brain and in Huntington’s disease, Brain Res. 199:147.PubMedCrossRefGoogle Scholar
  15. Epelbaum, J., Brazeau, P., Tsang, D., Brawer, J., and Martin, J. B., 1977, Subcellular distribution of radioimmunoassayable somatostatin in rat brain, Brain Res. 126:309.PubMedCrossRefGoogle Scholar
  16. Frenk, H., Urca, G., and Liebeskind, J. C., 1978, Epileptic properties of leucine- and methionine-enkephalin: Comparison with morphine and reversibility by naloxone, Brain Res. 147:327.PubMedCrossRefGoogle Scholar
  17. Gibbs, J., Young, R. C., and Smith, G. P., 1973, Cholecystokinin elecits satiety in rats with open gastric fistulas, Nature (London) 245:323.CrossRefGoogle Scholar
  18. Goldstein, A., Tachibana, S., Lowney, L. L., Hunkapiller, M., and Hood, L., 1979, Dynorphin-(1–13), an extraordinarily potent opioid peptide, Proc. Natl. Acad. Sci. USA 76:6666.PubMedCrossRefGoogle Scholar
  19. Goodman, R. R., Snyder, S. H., Kuhar, M. J., and Young, W. S., III, 1980, Differentiation of delta and mu opiate receptor localizations by light microscopic autoradiography, Proc. Natl. Acad. Sci. USA 77:6239.PubMedCrossRefGoogle Scholar
  20. Havrankova, J., Roth, J., and Brownstein, M., 1978, Insulin receptors are widely distributed in the central nervous system of the rat, Nature (London) 272:827.CrossRefGoogle Scholar
  21. Henry, J. L., 1976, Effects of substance P on functionally identified units in cat spinal cord, Brain Res. 114:439.PubMedCrossRefGoogle Scholar
  22. Hökfelt, T., Elde, R. P., Johansson, O., Ljungdahl, A., Schultzberg, M., Fuxe, K., Goldstein, M., Nilsson, G., Pernow, B., Terenius, L., Ganten, D., Jeffcoate, S. L., Rehfeld, J., and Said, S., 1978, Distribution of peptide-containing neurons, in: Psychopharmacology: A Generation of Progress (M. A. Lipton, A. DiMascio, and K. F. Killam, eds.), pp. 39–66, Raven Press, New York.Google Scholar
  23. Hökfelt, T., Johansson, O., Ljungdahl, A., Lundberg, J. M., and Schultzberg, M., 1980, Peptidergic neurons, Nature (London) 284:515.CrossRefGoogle Scholar
  24. Hughes, J., Smith, T. W., Kosterlitz, H. W., Fotergill, L. A., Morgan, B. A., and Morris, H. R., 1975, Identification of two related pentapeptides from the brain with potent opiate agonist activity, Nature (London) 258:577.CrossRefGoogle Scholar
  25. Ioffe, S., Havlicek, V., Friesen, H., and Chernick, V., 1978, Effect of somatostatin (SRIF) and L-glutamate on neurons of the sensorimotor cortex in awake habituated rabbits, Brain Res. 153:414.PubMedCrossRefGoogle Scholar
  26. Iversen, L. L., Iversen, S. D., Bloom, F., Douglas, C., Brown, M., and Vale, W., 1978, Calcium-dependent release of somatostatin and neurotensin from rat brain in vitro, Nature(London 273:161.CrossRefGoogle Scholar
  27. Jackson, I. M. D., 1980, Significance and function of neuropeptides in cerebrospinal fluid, in: Neurobiology of Cerebrospinal Fluid, Vol. 1 (J. H. Wood, ed.), pp. 625–650, Plenum Press, New York.Google Scholar
  28. Jessell, T. M., 1981, The role of substance P in sensory transmission and pain perception, in: Neurosecretion and Brain Peptides: Implication for Brain Function and Neurological Disease (J. B. Martin, S. Reichlin, and K. L. Bick, eds.), pp. 189–197, Raven Press, New York.Google Scholar
  29. Kovacs, G. I., Bohus, B., and Versteeg, D. H. G., 1979, The effects of vasopressin on memory processes: The role of noradrenergic neurotransmission, Neuroscience 4:1529.PubMedCrossRefGoogle Scholar
  30. Krieger, D. M., and Martin, J. B., 1981, Brain peptides, N. Engl. J. Med. 304:876, 944.PubMedCrossRefGoogle Scholar
  31. Land, H., Shutz, G., Schmale, H., and Richter, D., 1982, Nucleotide sequence of cloned cDNA encoding bovine arginine vasopressin-neurophysin II precursor, Nature (London) 295:299.CrossRefGoogle Scholar
  32. Legros, J. J., Gilot, P., Seron, X., Ciaessens, J., Adam, A., Moeglen, J. M., Audibert, A., and Berchier, P., 1978, Influence of vasopressin on learning and memory, Lancet I:41.CrossRefGoogle Scholar
  33. LeRoith, D., Shiloach, J., Roth, J., and Lesniak, M. A., 1980, Evolutionary origins of vertebrate hormones: Substances similar to mammalian insulins are native to unicellular eukaryotes (Te-trahymena/Neurospora), Proc. Natl. Acad. Sci. USA 77:6184.CrossRefGoogle Scholar
  34. LeRoith, D., Shiloach, J., Liotta, A. S., Krieger, D. T., Lewis, M., and Pert, C. B., 1981, Evolutionary origins of vertebrate hormones: Material very similar to adrenocorticotropic hormone, β-endorphin and dynorphin in protozoa, Trans. Assoc. Am. Physicians 94:52.PubMedGoogle Scholar
  35. Mains, R. E., Eipper, B. A., and Ling, N., 1977, Common precursor to corticotropins and endorphins, Proc. Natl. Acad. Sci. USA 74:3014.PubMedCrossRefGoogle Scholar
  36. Margules, D. L., Moisset, B., Lewis, M. J., Shibuya, H., and Pert, C. B., 1978, Beta-endorphin is associated with overeating in genetically obese mice (ob/ob) and rats (fa/fa), Science 202:988.PubMedCrossRefGoogle Scholar
  37. Martin, J. B., and Landis, D. M. D., 1981, Potential implications of brain peptides in neurological disorders, in: Neurosecretion and Brain Peptides: Implications for Brain Function and Neurological Disease (J. B. Martin, S. Reichlin, and K. Bick, eds.), pp. 673–690, Raven Press, New York.Google Scholar
  38. Martin, J. B., Reichlin, S., and Brown, G. M., 1977, Clinical Neuroendocrinology, Davis, Philadelphia.Google Scholar
  39. Mudge, A. W., Leeman, S. E., and Fischbach, G. D., 1979, Enkephalin inhibits release of substance P from sensory neurons in culture and decreases action potential duration, Proc. Natl. Acad. Sci. USA 76:526.PubMedCrossRefGoogle Scholar
  40. Nakanishi, S., Inoue, A., Kita, T., Nakamura, M., Chang, A. C. Y., Cohen, S. N., and Numa, S., 1979, Nucleotide sequence of cloned cDNA for bovine corticotropin-β-lipotropin precursor, Nature (London) 278:423.CrossRefGoogle Scholar
  41. Nakao, K., Oki, S., Tanaka, I., Horii, K., Nakai, Y., Furui, T., Fukushima, M., Kuwayama, A., Kageyama, N., and Imura, H., 1980, Immunoreactive β-endorphin and adrenocorticotropin in human cerebrospinal fluid, J. Clin. Invest. 66:1383.PubMedCrossRefGoogle Scholar
  42. Nicoll, R. A., Schenker, C., and Leeman, S. E., 1980, Substance P as a transmitter candidate, Annu. Rev. Neurosci. 3:227.PubMedCrossRefGoogle Scholar
  43. Nutt, J. G., Mroz, E. A., Leeman, S. E., Williams, A. C., Engel, W. K., and Chase, T. N., 1980, Substance P in human cerebrospinal fluid: Reductions in peripheral neuropathy and autonomic dysfunction, Neurology 30:1280.PubMedGoogle Scholar
  44. Oku, J., Glick, Z., Shimomura, Y., Inoue, S., Bray, G. A., and Walsh, J., 1980, Cholecystokinin and obesity, Clin. Res. 28:281 (abstract).Google Scholar
  45. Oliveros, J. C., Jandali, M. K., Timsit-Berthier, M., Remy, R., Benghezal, A., Audibert, A., and Moeglen, J. M., 1978, Vasopressin in amnesia, Lancet 1:42.PubMedCrossRefGoogle Scholar
  46. Pacold, S. T., and Blackard, W. G., 1979, Central nervous system insulin receptors in normal and diabetic rats, Endocrinology 105:1452.PubMedCrossRefGoogle Scholar
  47. Patel, Y., Rao, K., and Reichlin, S., 1977, Somatostatin in human cerebrospinal fluid, N. Engl. J. Med. 296:529.PubMedCrossRefGoogle Scholar
  48. Pearse, A. G. E., 1969, The cytochemistry and ultrastructure of polypeptide hormone-producing cells of the APUD series and the embryologie, physiologic, and pathologic implications of the concept, J. Histochem. Cytochem. 17:303.PubMedCrossRefGoogle Scholar
  49. Pert, C. B., and Snyder, S. H., 1973, Opiate receptor: Demonstration in nervous tissue, Science 179:1011.PubMedCrossRefGoogle Scholar
  50. Phillis, J. W., and Kirkpatrick, J. R., 1980, The actions of motilin, luteinizing hormone releasing hormone, cholecystokinin, somatostatin, vasoactive intestinal peptide and other peptides on rat cerebral cortical neurons, Can. J. Physiol. Pharmacol. 58:612.PubMedCrossRefGoogle Scholar
  51. Randic, M., and Miletic, V., 1978, Depressant actions of methionine-enkephalin and somatostatin in cat dorsal horn neurones activated by noxious stimuli, Brain Res. 152:196.PubMedCrossRefGoogle Scholar
  52. Rehfeld, J., 1980, Cholecystokinin, Trends Neurosci. 3:65.Google Scholar
  53. Renaud, L. P., Martin, J. B., and Brazeau, P., 1975, Depressant action of TRH, LH-RH and somatostatin on activity of central neurons, Nature (London) 255:233.CrossRefGoogle Scholar
  54. Riskind, P., and Martin, J. B., 1982, Management of pituitary secretory adenomas, in: Harrison’s Principles of Internal Medicine, Vol. 3 (K. Isselbacher, R. D. Adams, E. Braunwald, J. B. Martin, R. G. Petersdorf, and J. Wilson, eds.), pp. 235–252, McGraw-Hill, New York.Google Scholar
  55. Roberts, J. L., and Herbert, E., 1977, Characterization of a common precursor to corticotropin and β-lipotropin: Identification of β-lipotropin peptides and their arrangement relative to corticotropin in the precursor synthesized in a cell-free system, Proc. Natl. Acad. Sci. USA 74:5300.PubMedCrossRefGoogle Scholar
  56. Saito, A., Sankaran, H., Goldfine, I. D., and Williams, J. A., 1980, Cholecystokinin receptors in the brain: Characterization and distribution, Science 208:1155.PubMedCrossRefGoogle Scholar
  57. Sandman, C. A., and Kastin, A. J., 1978, A behavioral strategy for the CNS actions of the neuropeptides, in: Current Studies of Hypothalamic Function, Vol. 2 (W. L. Veale and K. Lederis, eds.), pp. 163–174, Karger, Basel.Google Scholar
  58. Sandman, C. A., George, J., Walker, B. B., Nolan, J. D., and Kastin, A. J., 1976, Neuropeptide MSH/-ACTH 4–10 enhances attention in the mentally retarded, Pharmacol. Biochem. Behav. 5(Suppl. 1):23.PubMedCrossRefGoogle Scholar
  59. Schiller, P. W., Lipton, A., Horrobin, D. F., and Bodanszky, M., 1978, Unsulfated C-terminal 7-peptide of cholecystokinin: A new ligand of the opiate receptor, Biochem. Biophys. Res. Commun. 85:1332.PubMedCrossRefGoogle Scholar
  60. Schneider, B. S., Monahan, J. W., and Hirsch, J., 1979, Brain cholecystokinin and nutritional status in rats and mice, J. Clin. Invest. 64:1348.PubMedCrossRefGoogle Scholar
  61. Smith, G. P., and Gibbs, J., 1981, Brain-gut peptides and the control of food intake, in: Neurosecretion and Brain Peptides: Implication for Brain Function and Neurological Disease (J. B. Martin, S. Reichlin, and K. L. Bick, eds.), pp. 389–395, Raven Press, New York.Google Scholar
  62. Spindel, E. R., Wurtman, R. J., and Bird, E. D., 1980, Increased TRH content of the basal ganglia in Huntington’s disease, N. Engl. J. Med. 303:1235.PubMedGoogle Scholar
  63. Straus, E., and Yalow, R. S., 1979, Cholecystokinin in the brains of obese and nonobese mice, Science 203:68.PubMedCrossRefGoogle Scholar
  64. Swanson, L. W., and Sawchenko, P. E., 1980, Paraventricular nucleus: A site for the integration of neuroendocrine and autonomic mechanisms, Neuroendocrinology 31:410.PubMedCrossRefGoogle Scholar
  65. Swanson, L. W., Sawchenko, P. E., Wiegand, S. J., and Price, J. L., 1980, Separate neurons in the paraventricular nucleus project to the median eminence and to the medulla or spinal cord, Brain Res. 198:190.PubMedCrossRefGoogle Scholar
  66. Taylor, D. P., and Pert, C. B., 1979, Vasoactive intestinal polypeptide: Specific binding to rat brain membranes, Proc. Natl. Acad. Sci. USA 76:660.PubMedCrossRefGoogle Scholar
  67. Terry, L. C., Rorstad, O. P., and Martin, J. B., 1980, The release of biologically and immunologically reactive somatostatin from perifused hypothalamic fragments, Endocrinology 107:794.PubMedCrossRefGoogle Scholar
  68. Vale, W., Ling, N., Rivier, J., Villarreal, J., Rivier, C., Douglas, C., and Brown, M., 1976, Anatomic and phylogenetic distribution of somatostatin, Metabolism 25:1491.PubMedCrossRefGoogle Scholar
  69. Vale, W., Spiess, J., Rivier, C., and Rivier, J., 1981, Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and β-endorphin, Science 213:1394.PubMedCrossRefGoogle Scholar
  70. van Houten, M., and Posner, B. I., 1979, Insulin binds to brain blood vessels in vivo, Nature (London) 282:623.CrossRefGoogle Scholar
  71. van Houten, M., Posner, B. I., Kopriwa, B. M., and Brawer, J. R., 1979, Insulin binding sites localized to nerve terminals in rat median eminence and arcuate nucleus, Science 207:1081.CrossRefGoogle Scholar
  72. Vijayan, E., and McCann, S. M., 1979, Suppression of feeding and drinking activity in rats following intraventricular injection of thyrotropin releasing hormone (TRH), Endocrinology 100:1727.CrossRefGoogle Scholar
  73. Weingartner, H., Gold, P., Ballenger, J. C., Smallberg, S. A., Summers, R., Rubinow, D. R., Post, R. M., and Goodwin, F. K., 1981, Effects of vasopressin on human memory functions, Science 211:601.PubMedCrossRefGoogle Scholar
  74. Woods, S. C., Lotter, E. C., McKay, L. D., and Porte, D., Jr., 1979, Chronic intracerebroven-tricular infusion of insulin reduces food intake and body weight of baboons, Nature (London) 282:503.CrossRefGoogle Scholar
  75. Yaksh, T. L., Farb, D. H., Leeman, S. E., and Jessell, T. M., 1979, Intrathecal capsaicin depletes substance P in the rat spinal cord and produces prolonged thermal analgesia, Science 206:481.PubMedCrossRefGoogle Scholar
  76. Zimmerman, E. A., 1981, The organization of oxytocin and vasopressin pathways, in: Neurosecretion and Brain Peptides: Implications for Brain Functions and Neurological Diseases (J. B. Martin, S. Reichlin, and K. L. Bick, eds.), pp. 63–75, Raven Press, New York.Google Scholar

Copyright information

© Plenum Publishing Corporation 1984

Authors and Affiliations

  • Joseph B. Martin
    • 1
  1. 1.Department of Neurology, Massachusetts General HospitalHarvard Medical SchoolBostonUSA

Personalised recommendations