Advertisement

The Role of Progestins and Progesterone in Brain Function and Behavior

  • Bert S. Kopell

Abstract

The extensive use of synthetic progestins as components of contraceptive preparations has focused interest on the effects of these substances on the central nervous system and on behavior. Recently the effects of progesterone and its metabolites on behavior has been reviewed by Hamburg (1), who emphasized that major clinical problems often occur during the postpartum period, the premenstrual period and menopause. These are periods of not only profomd psychological meaning to the woman but also periods of dramatic changes in the levels of circulating sexual hormones, in general, and progesterone, in particular.

Keywords

Sexual Behavior Reticular Formation Seizure Threshold Paradoxical Sleep Hypothalamic Neuron 
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.
    Haimburg D.A.: Effects of Progesterone on Behavior. In Endocrines and the Central Nervous System. Edited by the Association for Research in Nervous and Mental Diseases. The Williams and Wilkins Co. 43:251–265 (1966).Google Scholar
  2. 2.
    Rothchild, I.: Interrelations between progesterone and the ovary, pituitary, and central nervous system and the control of ovulation and the regulation of progesterone secretion. Vitamins and Hormones 23:209–327 (1965).CrossRefGoogle Scholar
  3. 3.
    Flerko, B.: Control of gonadotropin secretion in the female. In Neuroendocrinology. Ed. L. Martini and W.F. Ganong. Academic Press, New York, 613–688 (1966).Google Scholar
  4. 4.
    Woodbury, L.A. and Swinyard, C.A.: Stimulus parameters for electroshock seizures in rats. Am. J. Physiol. 170:661–667 (1950).Google Scholar
  5. 5.
    Woodbury, D.M. and Vemadakis, A.: Influence of hormones on brain activity. In Neuroen docrinology. Ed. Martini and Ganong. Academic Press, New York, 335–375 (1967).Google Scholar
  6. 6.
    Spiegel, E.A. and Wyeis, H.: Anticonvulsant effects of steroids. J. Lab. Clin. Med. 30:947–953 (1945).Google Scholar
  7. 7.
    Woolley, D.E. and Timiras, P.S.: The gonad-brain relationship: effects of female sex hormones on electroshock convulsions in the rat. Endocrinology 70:196–209 (1962).PubMedCrossRefGoogle Scholar
  8. 8.
    Stitt, S.L. and Kinnard, W.J.: The effect of certain progestins on the threshold of electrically-induced seizure patterns. Neurology 18:213–216 (1968).PubMedGoogle Scholar
  9. 9.
    Laidlaw, J.: Catamenial epilepsy. Lancet ii:1235–1237 (1956).CrossRefGoogle Scholar
  10. 10.
    Logothetis, J., Hamer, R., Morel, F. and Torres, F.: The role of estrogens and catamenial exacerbations of epilepsy. Neurology 9:352–360 (1959).PubMedGoogle Scholar
  11. 11.
    Cashin, M.F. and Moravek, V.: Physiological action of cholesterol. Am. J. Physiol. 82:294 (1927).Google Scholar
  12. 12.
    Selye, H.: Anesthetic effect of steroid hormones. Proc. Soc. Exp. Biol. Med. 46:116 (1941).Google Scholar
  13. 13.
    Merryman, W.: Progesterone anesthesia in hmnan subjects. J. Clin Endocrin. 14:1567 (1954).CrossRefGoogle Scholar
  14. 14.
    Gyermek, L.: Pregnanolone: a highly potent naturally occurring hypnotic anesthetic agent. Soc. Exp. Biol. Med. Proc. 125:1058–1062 (1967).Google Scholar
  15. 15.
    Gyermek, L., Genther, G. and Filming, N.: Some effects of progesterone and related steroids on the central nervous system. Int. J. Neuropharmacol. 6:191–198 (1967).PubMedCrossRefGoogle Scholar
  16. 16.
    Meyerson, B.J.: Relationship between the anesthetic and gestagenic action and estrous behavior inducing activity of different progestins. Endocrinology 81:369–374 (1967).PubMedCrossRefGoogle Scholar
  17. 17.
    Heuser, G., Ling, G.M. and Cluver, M.: Sleep induction by progesterone in the pre-optic area of cats. Electroenceph. Clin. Neurophysiol. 22:122–127 (1967).PubMedCrossRefGoogle Scholar
  18. 18.
    Lindsley, D. and Rubenstein, B.B.: Relationship between brain potentials and some other physiological variables. Proc. Soc. Exp. Biol. Med. 35:558 (1937).Google Scholar
  19. 19.
    Dusser de Barrenne, D. and Gibbs, F.A.: Variations in electroencephalogram during the menstrual cycle. Am. J. Obstet. Gynecol. 44: 687–690 (1942).Google Scholar
  20. 20.
    Gibbs, F.A. and Reid, D.E.: Electroencephalogram in pregnancy. Am. J. Obstet. Gynecol. 44:672–675 (1942).Google Scholar
  21. 21.
    Cress, C.H. and Greenblatt, M.: Absence of alteration in the EEC with stilbesterol and progesterone. Proc. Soc. Exp. Biol. Med. 60:139 (1945).PubMedGoogle Scholar
  22. 22.
    Arai, Y., Horoi, M., Mitra, J. and Gorski, R.A.: Influence of intravenous progesterone administration on the cortical electroencephalogram of the female rat. Neuroendocrinology 2:275–282 (1967).CrossRefGoogle Scholar
  23. 23.
    Bayer, C., Ramirez, V.D., Whitmoyer, D.I. and Sawyer, C.H. Effects of hormones on electrical activity of the brain in the rat and rabbit. Experimental Neurology 18:313–326 (1967).CrossRefGoogle Scholar
  24. 24.
    Matsumoto, S., Sato, I., Ito, T. and Matsuoka, A.: Electroencephalographic changes during long term treatment with oral contraceptives. International Journal of Fertility 11:195- 204 (1966).PubMedGoogle Scholar
  25. 25.
    Sawyer, C.H. and Kawakami, M.: Characteristics of behavioral and electroencephalographic after-reactions to copulation and vaginal stimulation in the female rabbit. Endocrinology 65:622–630 (1959).PubMedCrossRefGoogle Scholar
  26. 26.
    Porter, R.W., Cavanaugh, E.B., Critchlow, B.V. and Sawyer, C.H.: Localized changes in electrical activity of the hypothalamus in estrous cats following vaginal stimulation. Am. J. Physiol. 189:145–151 (1957).PubMedGoogle Scholar
  27. 27.
    Barraclough, C.A.: Hypothalamic activation associated with stimulation of the vaginal cervix in proestrous rats. Anat. Record 136:159 (1960).Google Scholar
  28. 28.
    Kawakami, M. and Sawyer, C.H.: Conditioned induction of paradoxical sleep in the rabbit. Experimental Neurology 9:470 (1964).PubMedCrossRefGoogle Scholar
  29. 29.
    Kawakami, M. and Sawyer, C.H.: Induction of behavioral and electroencephalographic changes in the rabbit by hormone administration or brain stimulation. Endocrinology 65:631 (1959).PubMedCrossRefGoogle Scholar
  30. 30.
    Magoun, H.W.: The Waking Brain, Charles C. Thomas, Springfield, 111., 1958.CrossRefGoogle Scholar
  31. 31.
    Kawakami, M. and Sawyer, C.H.: Neuroendocrine correlates of changes in brain activity thresholds by sex steroids and pituitary hormones. Endocrinology 65:652–668 (1959).PubMedCrossRefGoogle Scholar
  32. 32.
    Kawakami, M. and Sawyer, C.H.: Effects of sex hormones and anti-fertility steroids on brain thresholds in the rabbit. Endocrinology 80: 857–871 (1967).PubMedCrossRefGoogle Scholar
  33. 33.
    Penfield, W. and Jasper, H: Epilepsy and the Functional Anatomy of the Human Brain. Little, Brown, Boston, 1954.Google Scholar
  34. 34.
    Barraclough, C.A. and Cross, B.A.: Unit activity in the hypothalamus of the cyclic female rat: effect of genital stimuli and progesterone J. Endocrin. 26:339–359 (1963).CrossRefGoogle Scholar
  35. 35.
    Cross, B.A. and Silver, I.A.: Effect of luteal hormone on the behavior of hypothalamic neurons in pseudopregnant rats. J. Endocrin. 31:251–263 (1965).CrossRefGoogle Scholar
  36. 36.
    Ramirez, V.D., Komisaruk, B.R., Whitmoyer, D.I. and Sawyer, C.H.: Effects of hormones and vaginal stimulation on the EEG and hypothalamic units in rats. Am. J. Physiol. 212:1376–1384 (1967).PubMedGoogle Scholar
  37. 37.
    Komisaruk, B.R., McDonald, P.G., Whitmoyer, D.I. and Sawyer C.H.: Effects of progesterone and sensory stimulation on EEG and neuronal activity in the rat. Experimental Neurology 19:494–507 (1967).PubMedCrossRefGoogle Scholar
  38. 38.
    Papez, J.W.: A proposed mechanism of emotions. A.M.A. Arch. Neurol. Psychiat. 18:725 (1937).Google Scholar
  39. 39.
    MacLean, P.D.: Studies on the limbic system (visceral brain) and their bearing on psychosomatic problems. In Recent Developments in Psychosomatic Medicineo Edo Wittkower, E.D. and Cleghorn, R, Lippincott, Philadelphia. 1954Google Scholar
  40. 40.
    Kawakami, M. and Terasawa, E.: Differential control of sex hormone and oxytocin upon evoked potentials in the hypothalamus and mid-brain reticular formation. Japanese Journal of Physiology 17:65–93 (1967).CrossRefGoogle Scholar
  41. 41.
    Goy, R.W. and Young, W.C.: Strain differences in the behavioral responses of female guinea pigs to alpha-oestradiol ben- zoate and progesterone Behavior 10:340–354 (1957).Google Scholar
  42. 42.
    Ring, J.R.: The estrogen-progesterone induction of sexual receptivity in the spayed female mouse. Endocrinology 34:269–275 (1944).CrossRefGoogle Scholar
  43. 43.
    Boling, J.L. and Blandau, R.J.: The estrogen-progesterone induction of mating responses in the spayed female rat. Endocrinology 25:359–371 (1939).CrossRefGoogle Scholar
  44. 44.
    Dempsey, E.W., Hertz, R. and Young, W.C.: The experimental induction of oestrus (sexual receptivity) in the normal and ovariectomized guinea pig. Am. J. Physiol. 16: 201–209 (1936).Google Scholar
  45. 45.
    Kent, G.C. and Liberman, M.J.: Induction of psychic oestrus in the hamster with progesterone administered via the lateral brain ventricle. Endocrinology 45:29–32 (1949).PubMedCrossRefGoogle Scholar
  46. 46.
    Robinson, T.J.; Quantitative studies on the hormonal induction of oestrus in spayed ewes. J. Endocrin. 12:163–173 (1955).CrossRefGoogle Scholar
  47. 47.
    Phoenix, C.H., Goy, R.W. and Young, W.C.: Sexual behavior: general aspects. In Neuroendocrinology Ed. Martini and Ganong. Academic Press, New York, 163–196 (1967).Google Scholar
  48. 48.
    Makepeace, A.W., Weinstein, G.L. and Friedman, M.H.: J. Physiol. 119:512–516 (1937).Google Scholar
  49. 49.
    Marshall, F.H.A. and Hammond, J.: Experimental control by hormone action of the oestrus cycle in the ferret. J. Endocrin. 4:159–168 (1945).CrossRefGoogle Scholar
  50. 50.
    Lunde, D.: Stimulation versus hormone induction of copu- latory behavior in female rats. Master of Arts thesis, Department of Psychology and Graduate Division, Stanford University, 1964.Google Scholar
  51. 51.
    Edwards, D.A., Whalen, R.E. and Nadler, R.D.: Induction of oestrus: estrogen-progesterone interactions. Physiology and Behavior 3:29–33 (1968).CrossRefGoogle Scholar
  52. 52.
    Sawyer, C.H. and Everett, J.W.: Stimulatory and inhibitory effects of progesterone on the release of pituitary ovulating hormone in the rabbit. Endocrinology 65:644–651 (1959).PubMedCrossRefGoogle Scholar
  53. 53.
    Zarrow, M.X., Grota, L.J. and Denenberg, V.H.: Maternal behavior in the rat: survival of new bom fostered yomg after hormonal treatment of the foster mother. Anat. Ree. 157:13–18.Google Scholar
  54. 54.
    Kislach and Beach; Inhibition of aggressiveness by ovarian hormones. Endocrinology 56:684–692 (1955).CrossRefGoogle Scholar
  55. 55.
    Campbell, H.J.: Acute effects of pregnane steroids on septal self-stimulation in the rabbit. J. Physiol. 196:134–135 (1968).Google Scholar
  56. 56.
    Overton, D.A.: Psychopharmacologia 10:6 (1966).PubMedCrossRefGoogle Scholar
  57. 57.
    Stewart, J., Krebs, W.H. and Kaczender, E.: State- dependent learning produced with steroids. Nature 216:1223–1224 (1967).PubMedCrossRefGoogle Scholar
  58. 58.
    Ball, J.: Sexual responsiveness in female monkeys after castration and subsequent estrin administration. Psychol. Bull. 33:811 (1936).Google Scholar
  59. 59.
    Michael, R.P., Herbert, J. and Welegalla, J.: Ovarian hormones and the sexual behavior of the male rhesus monkey under laboratory conditions J. Endocrin. 39: 81–98 (1965).CrossRefGoogle Scholar
  60. 60.
    Michael, R.P., Saayman, G.S. and Zumpe, D.: Inhibition of sexual receptivity by progesterone in rhesus monkeys. J. Endocrin. 39:309–310 (1967).CrossRefGoogle Scholar
  61. 61.
    McCance, R., Luff, M. and Widdowson, E.: The physical and emotional periodicity in women. J. Hygiene 37:571 (1937).CrossRefGoogle Scholar
  62. 62.
    59.Moos, R.H., Kopell, B.S., Melges, F.T., Yalom, I.D. Lunde, D.T., Clayton, R.B, and Hamburg, D.A.: Variations in symptoms and wood during the menstrual cycle. Psychosomatic Research (In press) (1968).Google Scholar
  63. 63.
    Benedek, T.F.: Sexual function in women and their disturbances. In American Handbook of Psychiatiry Ed. Arieti. Basic Books, Inc., 1959, 727–748.Google Scholar
  64. 64.
    Yerkes, R.M, and Elder, J.H.J.:Concerning reproduction in the chimpanzee. Science 81:542–543 (1937).CrossRefGoogle Scholar
  65. 65.
    Heller, C.G., Moore, D.J., Paulsen, C.A., Nelson, W.O. and Laidlaw, W.M.: Effects of progesterone and synthetic progestins on the reproductive physiology of normal men. Federation Proceedings 18:1057–1064 (1959).PubMedGoogle Scholar
  66. 66.
    Washburn, S.L. and De Vore, I.: The social life of baboons. Scient. Am. 204:62–71 (1961).CrossRefGoogle Scholar
  67. 67.
    Michael, R.P., Herbert, J. and Welegalla, J.: Ovarian hormones and grooming behavior in the rhesus monkey (macca mulatta) under laboratory conditions J. Endocrin. 36:263–279 (1966).CrossRefGoogle Scholar
  68. 68.
    Krus, D.M., Wapner, S., Bergen, J. and Freeman, H.: The g influence of progesterone on behavioral changes induced by lysergic acid diethylamide (LSD-25) in normal males. Psychopharmacologia 2:177–184 (1961).PubMedCrossRefGoogle Scholar
  69. 69.
    Yalom, I,: Unpublished observations.Google Scholar
  70. 70.
    Brown, J.B. and Matthew, G.D.: The application of urinary estrogen measurements to problems in gynecology. Ree. Prog. Horm. Res. 18:337 (1962).Google Scholar
  71. 71.
    VanderMolen, H.J., Runnebaum, B. and Nishizawa, E.E.: On the presence of progesterone in blood plasma from normal women. J. Clin. Endocrin. 25:170 (1965).CrossRefGoogle Scholar
  72. 72.
    Zander, J.: The chemical estimation of progesterone and its metabolites in body fluids and target organs. In Progesterone ed. by A.C. Barnes, 77–90 Brook Lodge Press, Augusta, Mich. 1961.Google Scholar
  73. 73.
    70.Lurie, A.O. and Weiss, J.B.: Progesterone in cerebrospinal fluid during human pregnancy. Nature 215:1178 (1931).CrossRefGoogle Scholar
  74. 74.
    Frank, R.T.: The hormonal causes of premenstrual tension. Arch. Neural. Psychiat. 26:1053 (1931).Google Scholar
  75. 75.
    Rogers, J.: Endocrine and Metabolic Aspects of Gynecology W.B. Saunders, Philadelphia, 1963.Google Scholar
  76. 76.
    72.Moos, R.H.: The development of a menstrual distress questionnaire. Psychosomatic Medicine, in press, 1968.Google Scholar
  77. 77.
    Dalton, K.: Menstruation and accidents. Brit. Med. J. 2:1425 (1960).PubMedCrossRefGoogle Scholar
  78. 78.
    Dalton, K.: Menstruation and acute psychiatric illness. Brit. Med. J. 1:148 (1959).PubMedCrossRefGoogle Scholar
  79. 79.
    Morton, J.H., Addison, H., Addison, R., Hunt, L. and Sullivan, J.: Clinical study of premenstrual tension. Am. J. Obstet. Gynecol. 65:1182 (1953).PubMedGoogle Scholar
  80. 80.
    Yalom, I., Lunde, D., Moos, R. and Hamburg, D.: The “postpartum blues” syndrome: description and related variables. Archives of General Psychiatry, in press, 1968.Google Scholar
  81. 81.
    Hamilton, J.: Postpartum Psychiatric Problems Mosby, St. Louis, Missouri, 1962.Google Scholar
  82. 82.
    Pugh, T.: Rates of mental disease related to child- bearing. New England Journal of Medicine 268:1224–1228 (1963).PubMedCrossRefGoogle Scholar
  83. 83.
    Heftmann, E. and Mosettig, E.: Biochemistry of Steroids Reinhold, New York, 1960.Google Scholar

Copyright information

© Plenum Press, New York 1969

Authors and Affiliations

  • Bert S. Kopell
    • 1
  1. 1.Department of PsychiatryStanford University School of MedicineUSA

Personalised recommendations