The Hippocampus and Regulation of the Hypothalamic-Hypophyseal-Adrenal Cortical Axis

  • Carol Van Hartesveldt


It has been established since 1950 that the hormones of the adrenal cortex are regulated by the central nervous system. The adrenal cortex is stimulated by adrenocorticotropic hormone (ACTH) carried through the circulatory system from the adenohypophysis, which is activated by corticotropin releasing factor (CRF) brought via the hypophyseal portal vessels from the median eminence of the hypothalamus. Many structures of the limbic system project to the hypothalamus and are therefore potential candidates for modulating adrenocortical hormone secretion. The hippocampus has been implicated in such a role since the late 1950s. The results of much of the research in this area have led many authors to conclude that the hippocampus inhibits hypothalamic mechanisms controlling the secretion of adrenal corticosteroid hormones. However, a close examination of the existing data reveals that this generalization is probably misleading oversimplification since (1) there is more than one functional system which has access to the final common path of adrenocortical steroid hormone secretion and (2) different methods of hippocampal disruption give results which lead to different conclusions about its function. In this chapter, the data relating to the role of the hippocampus in the regulation of this hormone system will be critically analyzed using these two points as an organizational framework.


Corticotropin Release Factor Median Eminence Plasma Corticosterone Hippocampal Lesion Plasma Corticosterone Level 
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  1. Barrett, A. M., Hodges, J. R., And Sayers, G. The Influence Of Sex, Adrenalectomy, And Stress On Blood Acth Levels In The Rat. Journal Of Endocrinology, 1957, 16, X III.Google Scholar
  2. Bohus, B., Nyakas, C., And Lissak, K. Involvement Of Suprahypothalamic Structures In The Hormonal Feedback Action Of Corticosteroids. Acta Physiologica Academiae Scientiarum Hungaricae, 1968, 34, 1–8.PubMedGoogle Scholar
  3. Coover, G. D., Goldman, L., And Levine, S. Plasma Corticosterone Levels During Extinction Of A Lever-Press Response In Hippocampectomized Rats. Physiology And Behavior, 1971, 7, 727–732.PubMedCrossRefGoogle Scholar
  4. Critchlow, V. The Role Of Light In The Neuroendocrine System. In A. V. Nalbandov (Ed.), Advances in neuroendocrinology. Urbana: University of Illinois Press, 1963, pp. 377–402.Google Scholar
  5. Dallman, M. F., And Yates, F. E. Anatomical And Functional Mapping Of Central Neural Input And Feedback Pathways Of The Adrenocortical System. In V. H. T. James And J. Landon (Eds.), The investigation of hypothalamic-pituitary-adrenalfunction. Cambridge: University Press, 1968, pp. 39–72.Google Scholar
  6. Davidson, J. M., And Feldman, S. Effects Of Extrahypothalamic Dexamethasone Implants On The Pituitary-Adrenal System. Acta Endocrinologica, 1967, 55, 240–246.PubMedGoogle Scholar
  7. Dupont, A., Bastarache, E., Endroczi, E., And Fortier, C. Effect Of Hippocampal Stimulation On The Plasma Thyrotropin (THS) and corticosterone responses to acute cold exposure in the rat. Canadian Journal of Physiology and Pharmacology, 1972, 50, 364–367.PubMedCrossRefGoogle Scholar
  8. Endroczi, E., And Lissak, K. Interrelations Between Paleocortical Activity And Pituitary-Adrenocortical Function. Acta Physiologica Academiae Scientiarum Hungaricae, 1962, 21, 257–263.Google Scholar
  9. Endroczi, E., Lissak, K., Bohus, B., And Kovacs, S. The Inhibitory Influence Of Archicortical Structures On Pituitary-Adrenal Function. Acta Physiologica Academiae Scientiarum Hungaricae, 1959, 16, 17–22.Google Scholar
  10. Feldman, S., Conforti, N., And Chowers, I. Effects Of Partial Hypothalamic Deafferentations On Adrenocortical Responses. Acta Endocrinologica, 1972, 69, 526–530.PubMedGoogle Scholar
  11. Fendler, K., Karmos, G., And Telegdy, G. The Effect Of Hippocampal Lesion On Pituitary-Adrenal Function. Acta Physiologica Academiae Scientiarum Hungaricae, 1961, 20, 293–297.PubMedGoogle Scholar
  12. Gemzell, C. A., Van Dyke, D. C., Tobias, C. A., And Evans, H. M. Increase In Formation And Secretion Of Acth Following Adrenalectomy. Endocrinology, 1951, 49, 325–336.PubMedCrossRefGoogle Scholar
  13. Gerlach, J. L., And McEwen, B. S. Rat Brain Binds Adrenal Steroid Hormone: Radioautography Of Hippocampus With Corticosterone. Science, 1972, 175, 1133–1136.PubMedCrossRefGoogle Scholar
  14. Halasz, B., Slusher, M. A., And Gorski, R. A. Adrenocorticotrophic Hormone Secretion In Rats After Partial Or Total Interruption Of Neural Afferents To The Medial Basal Hypothalamus. Neuroendocrinology, 1967, 2, 43–55.CrossRefGoogle Scholar
  15. Hiroshige, T., And Sakakura, M. Circadian Rhythm Of Corticotropin-Releasing Activity In The Hypothalamus Of Normal And Adrenalectomized Rats. Neuroendocrinology, 1971, 7, 25–36.PubMedCrossRefGoogle Scholar
  16. Hiroshige, T., And Sato, T. Changes In Hypothalamic Content Of Corticotropin-Releasing Activity Following Stress During Neonatal Maturation In The Rat. Neuroendocrinology, 1971, 7, 257–270.PubMedCrossRefGoogle Scholar
  17. Hodges, J. R. The Hypothalamus And Pituitary Acth Release. Progress In Brain Research, 1970, 32, 12–18.PubMedCrossRefGoogle Scholar
  18. Iuvone, P. M., And Van Hartesveldt, C. Locomotor Activity And Plasma Corticosterone In Rats With Hippocampal Lesions. In Preparation.Google Scholar
  19. Jackson, W. J., And Regestein, Q. R. Hippocampectomy In Rhesus Monkeys: Effects On Plasma Cortisol During Two Stressful Conditions. Paper Presented At The Society For Neuroscience Fourth Annual Meeting, St. Louis, October 1974.Google Scholar
  20. Kawakami, M., Koshino, T., And Hattori, Y. Changes In The Eeg Of The Hypothalamus And Limbic System After Administration Of Acth, Su-4885 And Ach In Rabbits With Special Reference To Neurohumoral Feedback Regulation Of Pituitary-Adrenal System. Japanese Journal Of Physiology, 1966, 16, 551–569.PubMedCrossRefGoogle Scholar
  21. Kawakami, M., Seto, K., Terasawa, E., Yoshida, K., Miyamoto, T., Sekiguchi, M., And Hattori, Y. Influence Of Electrical Stimulation And Lesion In Limbic Structure Upon Biosynthesis Of Adreno-Corticoid In The Rabbit. Neuroendocrinology, 1968A, 3, 337–348.CrossRefGoogle Scholar
  22. Kawakami, M., Seto, K., And Yoshida, K. Influence Of Corticosterone Implantation In Limbic Structure Upon Biosynthesis Of Adrenocortical Steroid. Neuroendocrinology, 1968B, 3, 349–354.Google Scholar
  23. Kearley, R. C., Van Hartesveldt, C., And Woodruff, M. L. Behavioral And Hormonal Effects Of Hip-Pocampal Lesions On Male And Female Rats. Physiological Psychology, 1974, 2, 187–196.Google Scholar
  24. Kim, C., And Kim, C. U. Effect Of Partial Hippocampal Resection On Stress Mechanism In Rats. American Journal Of Physiology, 1961, 201, 337–340.PubMedGoogle Scholar
  25. Knigge, K. M. Adrenocortical Response To Stress In Rats With Lesions In Hippocampus And Amygdala. Proceedings Of The Society For Experimental Biology And Medicine, 1961, 108, 18–21.PubMedGoogle Scholar
  26. Knigge, K. M. Feedback Mechanisms In Neural Control Of Adenohypophyseal Function: Effect Of Steroids Implanted In Amygdala And Hippocampus. Abstracts Of The Second International Congress On Hormonal Steroids, Excerpta Medica International Congress Series No. Ill, 1966, P. 208.Google Scholar
  27. Knigge, K. M., And Hays, M. Evidence Of Inhibitive Role Of Hippocampus In Neural Regulation Of Acth Release. Proceedings Of The Society For Experimental Biology And Medicine, 1963, 114, 67–69.PubMedGoogle Scholar
  28. Knizley, H., Jr. The Hippocampus And Septal Area As Primary Target Sites For Corticosterone. Journal Of Neurochemistry, 1972, 19, 2737–2745.PubMedCrossRefGoogle Scholar
  29. Lanier, L. P., Van Hartesveldt, C., Weis, B., And Isaacson, R. L. Effects Of Differential Hippocampal Damage Upon Rhythmic And Stress-Induced Corticosterone Secretion In The Rat. Neuroendocrinology, 1975, In Press.Google Scholar
  30. Lengvari, I., And Halasz, B. Evidence For A Diurnal Fluctuation In Plasma Corticosterone Levels After Fornix Transection In The Rat. Neuroendocrinology, 1973, 11, 191–196.PubMedCrossRefGoogle Scholar
  31. Makara, G. B., Stark, E., Palkovits, M., Revesz, T., And Mihaly, K. Afferent Pathways Of Stressful Stimuli: Corticotrophin Release After Partial Deafferentation Of The Medial Basal Hypothalamus. Journal Of Endocrinology, 1969, 44, 187–193.PubMedCrossRefGoogle Scholar
  32. Makara, G. B., Stark, E., And Palkovits, M. Afferent Pathways Of Stressful Stimuli: Corticotropin Release After Hypothalamic Deafferentation. Journal Of Endocrinology, 1970, 47, 411–416.PubMedCrossRefGoogle Scholar
  33. Mandell, A., Chapman, L. F., Rand, R. W., And Walter, R. D. Plasma Corticosteroids: Changes In Concentration After Stimulation Of Hippocampus And Amygdala. Science, 1963, 139, 1212.PubMedCrossRefGoogle Scholar
  34. Mason, J. W. The Central Nervous System Regulation Of Acth Secretion. In H. H. Jasper, L. D. Proctor, R. S. Knighton, W. C. Noshay, And R. T. Costello (Eds.), Reticular formation of the brain. Boston: Little, Brown, 1957, pp. 645–670.Google Scholar
  35. Mason, J. W. Psychological Influences On The Pituitary-Adrenal Cortical System. Recent Progress In Hormone Research, 1959, 15, 345–389.Google Scholar
  36. Mason, J. W. A Review Of Psychoendocrine Research On The Pituitary-Adrenal Cortical System. Psychosomatic Medicine, 1968, 30, 576–607.PubMedGoogle Scholar
  37. McEwen, B. S., And Weiss, J. M. The Uptake And Action Of Corticosterone: Regional And Subcellular Studies On Rat Brain. Progress In Brain Research, 1970, 32, 200–210.PubMedCrossRefGoogle Scholar
  38. McEwen, B. S., Weiss, J. M., And Schwartz, L. S. Selective Retention Of Corticosterone By Limbic Structure In Rat Brain. Nature (London), 1968, 220, 911–912.CrossRefGoogle Scholar
  39. McEwen, B. S., Weiss, J. M., And Schwartz, L. S. Uptake Of Corticosterone By Rat Brain And Its Concentration By Certain Limbic Structures. Brain Research, 1969, 16, 227–241.PubMedCrossRefGoogle Scholar
  40. McEwen, B. S., Weiss, J. M., And Schwartz, L. S. Retention Of Corticosterone By Cell Nuclei From Brain Regions Of Adrenalectomized Rats. Brain Research, 1970, 17, 471–482.PubMedCrossRefGoogle Scholar
  41. Mess, B., And Martini, L. The Central Nervous System And The Secretion Of Anterior Pituitary Trophic Hormones. In V. H. T. James (Ed.), Recent advances in endocrinology. Boston: Little, Brown, 1968, pp. 1–49.Google Scholar
  42. Moberg, G. P., Scapagnini, U., De Groot, J., and Ganong, W. F. Effect of sectioning the fornix on diurnal fluctuation in plasma corticosterone levels in the rat. Neuroendocrinology, 1971, 7, 11–15.PubMedCrossRefGoogle Scholar
  43. Motta, M., Piva, F., and Martini, L. The role of “short” feedback mechanisms in the regulation of ad-renocorticotropin secretion. Progress in Brain Research, 1970, 32, 25–32.PubMedCrossRefGoogle Scholar
  44. Nakadate, G. M., and De Groot, J. Fornix transection and adrenocortical function in rats. Anatomical Record, 1963, 145, 338.Google Scholar
  45. Ondo, J. G., and Kitay, J. I. Pituitary-adrenal function in rats with diencephalic islands. Neuroendocrinology, 1972, 9, 72–82.PubMedCrossRefGoogle Scholar
  46. Palka, Y., Coyer, D., and Critchlow, V. Effects of isolation of medial basal hypothalamus on pituitary-adrenal and pituitary-ovarian functions. Neuroendocrinology, 1969, 5, 333–349.PubMedCrossRefGoogle Scholar
  47. Pfaff, D. W., Silva, M. T. A., and Weiss, J. M. Telemetered recording of hormone effects on hippocampal neurons. Science, 1971, 172, 394–395.PubMedCrossRefGoogle Scholar
  48. Porter, R. W. The central nervous system and stress-induced eosinopenia. Recent Progress in Hormone Research, 1954, 10, 1–27.Google Scholar
  49. Rubin, R. T., Mandell, A. J., and Crandall, P. H. Corticosteroid responses to limbic stimulation in man: Localization of stimulus sites. Science, 1966, 153, 767–768.Google Scholar
  50. Seggie, J. A., Brown, G. M., Uhlin, I. V., Schally, A., and Kastin, A. J. Effect of septal lesions on plasma levels of corticosterone, growth hormone, prolactin and melanocyte stimulating hormone before and after stimulation. Paper presented at the Society for Neuroscience Third Annual Meeting, San Diego, November 1973.Google Scholar
  51. Seiden, G. and Brodish, A. Physiological evidence for “short-loop” feedback effects of ACTH on hypothalamic CRF. Neuro endocrinology, 1971, 8, 154–164.Google Scholar
  52. Slusher, M. A. Effects of chronic hypothalamic lesions on diurnal and stress corticosteroid levels. American Journal of Physiology, 1964, 206, 1161–1164.PubMedGoogle Scholar
  53. Slusher, M. A. Effects of Cortisol implants in the brain stem and ventral hippocampus on diurnal corticosteroid levels. Experimental Brain Research, 1966, 1, 184–194.CrossRefGoogle Scholar
  54. Slusher, M. A., and Hyde, J. F. Effects of limbic stimulation on release of corticosteroids into the adrenal venous effluent of the cat. Endocrinology, 1961, 69, 1080–1084.PubMedCrossRefGoogle Scholar
  55. Steiner, F. A., Ruf, K., and Akert, K. Steroid-sensitive neurons in rat brain: Anatomical localization and response to neurohumours and ACTH. Brain Research, 1969, 12, 74–85.PubMedCrossRefGoogle Scholar
  56. Stevens, W., Grosser, B. I., and Reed, D. J. Corticosterone-binding molecules in rat brain cytosols: Regional distribution. Brain Research, 1971, 35, 602–607.Google Scholar
  57. Takebe, K., Sakakura, M., and Mashimo, K. Continuance of diurnal rhythmicity of CRF activity in hypophysectomized rats. Endocrinology, 1972, 90, 1515–1520.PubMedCrossRefGoogle Scholar
  58. Wilson, M., and Critchlow, V. Effect of fornix transection or hippocampectomy on rhythmic pituitary-adrenal function in the rat. Neuro endocrinology, 1973/1974, 13, 29–40.Google Scholar
  59. Zimmerman, E., and Critchlow, V. Effects of diurnal variation in plasma corticosterone levels on adrenocortical response to stress. Proceedings of the Society for Experimental Biology and Medicine, 1967, 125, 658–663.Google Scholar

Copyright information

© Plenum Press, New York 1975

Authors and Affiliations

  • Carol Van Hartesveldt
    • 1
  1. 1.University of FloridaGainesvilleUSA

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