Sex and the Brain

Overview

This collection of foundational papers on sex differences in the brain traces the development of a much-invoked, fast-growing young field at the intersection of brain and behavior. The reader is introduced to the meaning and nature of sexual dimorphisms, the mechanisms and consequences of steroid hormone action, and the impact of the field on interpretations of sexuality and gender.

Building on each other in point-counterpoint fashion, the papers tell a fascinating story of an emerging science working out its core assumptions. Experimental and theoretical papers, woven together by editor's introductions, open a window onto knowledge in the making and a vigorous debate between reductionist and pluralist interpreters.

Five major sections include papers on conceptual and methodological background, central nervous system dimorphisms, mechanisms for creating dimorphisms, dimorphisms and cognition, and dimorphisms and identity. Each section builds from basic concepts to early experiments, from experimental models to humans, and from molecules to mind. Papers by such leading scholars as Arthur Arnold, Frank Beach, Anne Fausto-Sterling, Patricia Goldman-Rakic, Doreen Kimura, Simon LeVay, Bruce McEwen, Michael Merzenich, Bertram O'Malley, Geoffrey Raisman, and Dick Swaab, illustrate a rich blend of perspectives, approaches, methods, and findings.

Sex and the Brain will show students how a scientific paper can be analyzed from many perspectives, and supply them with critical tools for judging a rapidly emerging science in a contentious area.

Table of Contents

  1. Acknowledgements
  2. Preface
  3. I. BACKGROUND/INTRODUCTION The Concept of Sexual Dimorphisms
  4. 1. Sexually dimorphic behavior: Definition and the organizational hypothesis. In R. W. Goy and B. S. McEwen (Eds.), Sexual Differentiation of the Brain: Based on a Work Session of the Neurosciences Research Program. MIT Press, Cambridge, pp. 1–12.

    Robert W. Goy and Bruce S. McEwen (1980)

  5. 2. Sex differences in behavior: Rodents, birds, and primates. In R. W. Goy and B. S. McEwen (Eds.), Sexual Differentiation of the Brain: Based on a Work Session of the Neurosciences Research Program. MIT Press, Cambridge, pp. 13–58.

    Robert W. Goy and Bruce S. McEwen (1980)

  6. 3. Female mating behavior shown by male rats after administration of testosterone propionate. Endocrinology 29: 409–412.

    Frank A. Beach (1941)

  7. 4. Masculine copulatory behavior in intact and castrated female rats. Endocrinology 31: 393–409.

    Frank A. Beach and Priscilla Rasquin (1942)

  8. 5. An urge to explain the incomprehensible: Geoffrey Harris and the discovery of the neural control of the pituitary gland. Annual Review of Neuroscience 20: 533–566.

    G. Raisman (1997)

  9. 6. The induction of ovulation in the rabbit, by electrical stimulation of the hypothalmohypophysial mechanism. Proceedings of the Royal Society of London B 612: 374–394.

    G. W. Harris (1937)

  10. 7. Proliferative capacity of the hypophysial portal vessels. Nature 165: 854.

    G. W. Harris and Dora Jacobsohn (1950)

  11. 8. The effect of intrapituitary infusion of median eminence and other brain extracts on anterior pituitary gonadotrophic secretion. Journal of Physiology 170: 474–486.

    H. J. Campbell, G. Feuer, and G. W. Harris (1964)

  12. 9. Sexual differentiation of the central nervous system. Science 211: 1294–1302.

    Neil J. MacLusky and Frederick Naftolin (1981)

  13. 10. A gene from the human sexdetermining region encodes a protein with homology to a conserved DNA-binding motif. Nature 346: 240–244.

    Andrew H. Sinclair, Philippe Berta, Mark S. Palmer, J. Ross Hawkins, Beatrice L. Griffiths, Matthijs J. Smith, Jamie W. Foster, Anna-Maria Frischauf, Robin Lovell-Badge, and Peter N. Goodfellow (1990)

  14. 11. Molecular basis of mammalian sexual determination: Activation of Mullerian inhibiting substance gene expression by SRY. Science 266: 1494–1500.

    Christopher M. Haqq, Chih-Yen King, Etsuji Ukiyama, Sassan Falsafi, Tania N. Haqq, Patricia K. Donahoe, and Michael A. Weiss (1995)

  15. 12. Exchange of terminal portions of X- and Y- chromosomal short arms in human XX males. Nature 328: 437–440.

    David C. Page, Laura G. Brown, and Albert de la Chapelle (1987)

  16. 13. Steroid 5-alphareductase deficiency in man: An inherited form of male pseudohermaphroditism. Science 186: 1213–1215.

    Julianne Imperato-McGinley, Luis Guerrero, Teofilo Gautier, and Ralph E. Peterson (1974)

  17. 14. Phenotypic features, androgen receptor binding, and mutational analysis in 278 clinical cases reported as androgen insensitivity syndrome. Journal of Clinical Endocrinology and Metabolism 85: 658–665.

    S. F. Ahmed, A. Cheng, L. Dovey, J. R. Hawkins, H. Martin, J. Rowland, N. Shimura, A. D. Tait, and I. A. Hughes (2000)

  18. 15. 47,XXY female with testicular feminization and positive SRY: A case report. Journal of Reproductive Medicine 50: 138–140.

    Eloisa Saavedra-Castillo, Elvia I. Cortes-Gutierrez, Martha I. Davila-Rodriguez, Maria Eugenia Reyes-Martinez, and Amalia Oliveros-Rodriguez (2005)

  19. 16. The five sexes: Why male and female are not enough. The Sciences 33: 20–24.

    Anne Fausto-Sterling (1993)

  20. 17. Estrogen formation in the mammalian brain: Possible role of aromatase in sexual differentiation of the hippocampus and neocortex. Steroids 50: 459–474.

    Neil J. MacLusky, Ann S. Clark, Frederick Naftolin, and Patricia S. Goldman-Rakic (1987)

  21. 18. Molecular mechanisms of action of steroid/thyroid receptor superfamily. Annual Review of Biochemistry 63: 451–486.

    Ming-Jer Tsai and Bert W. O'Malley (1994)

  22. 19. Inhibition of rat sexual behavior by antisense oligonucleotides to the progesterone receptor. Endocrinology 135: 1409–1414.

    Shailaja K. Mani, Jeffrey D. Blaustein, Jamie M. C. Allen, Simon W. Law, Bert W. O'Malley, and James H. Clark (1994)

  23. 20. Hormonal regulation of hypothalamic gene expression: Identification of multiple novel estrogen induced genes. Journal of Steroid Biochemistry and Molecular Biology 51: 131–136.

    Simon W. Law, Ede M. Apostolakis, Patrick J. Samora, Bert W. O'Malley, and James H. Clark (1994)

  24. 21. Estrogen resistance caused by a mutation in the estrogenreceptor gene in a man. New England Journal of Medicine 331: 1056–1061.

    Eric P. Smith, Jeff Boyd, Graeme R. Frank, Hiroyuki Takahashi, Robert M. Cohen, Bonny Specker, Timothy C. Williams, Dennis B. Lubahn, and Kenneth S. Korach (1994)

  25. 22. Organizing action of prenatally administered testosterone propionate on the tissues mediating mating behavior in the female guinea pig. Endocrinology 65: 369–382.

    Charles H. Phoenix, Robert W. Goy, Arnold A. Gerall, and William C. Young (1959)

  26. 23. Hormones and sexual behavior. Science 143: 212–218.

    William C. Young, Robert W. Goy, and Charles H. Phoenix (1961)

  27. 24. Neonatal androgens influence the social play of prepubescent rats. Hormones and Behavior 15: 197–213.

    Michael J. Meany and Jane Stewart (1981)

  28. II. CENTRAL NERVOUS SYSTEM DIMORPHISMS The Song Bird
  29. 25. Sexual dimorphism in vocal control areas of the songbird brain. Science 194: 211–213.

    Fernando Nottebohm and Arthur P. Arnold (1976)

  30. 26. Testosterone triggers growth of brain vocal control nuclei in adult female canaries. Brain Research 189: 429–436.

    Fernando Nottebohm (1980)

  31. 27. Altered perception of speciesspecific song by female birds after lesions of a forebrain nucleus. Science 251: 303–305.

    Eliot A. Brenowitz (1991)

  32. 28. Hormone accumulation in a sexually dimorphic motor nucleus of the rat spinal cord. Science 210: 564–566.

    S. Marc Breedlove and Arthur P. Arnold (1980)

  33. 29. Hormonal control of a developing neuromuscular system. I. Complete demasculinization of the male rat spinal nucleus of the bulbocavernosus using the anti-androgen flutamide. Journal of Neuroscience 3: 417–423.

    S. Marc Breedlove and Arthur P. Arnold (1983)

  34. 30. Sexual dimorphism in human and canine spinal cord: Role of early androgen. Proceedings of the National Academy of Sciences USA 83: 7527–7531.

    Nancy G. Forger and S. Marc Breedlove (1986)

  35. 31. Sexual dimorphism in the neuropil of the preoptic area of the rat and its dependence on neonatal androgen. Brain Research 54: 1–29.

    G. Raisman and P. M. Field (1973)

  36. 32. Sex difference in the bed nucleus of the stria terminalis of the human brain. Journal of Comparative Neurology 302: 697–706.

    Laura S. Allen and Roger A. Gorski (1990)

  37. 33. Evidence for a morphological sex difference within the medial preoptic area of the rat brain. Brain Research 148: 333–346.

    R. A. Gorski, J. H. Gordon, J. E. Shryne, and A. M. Southam (1978)

  38. 34. A sexually dimorphic nucleus in the human brain. Science 228: 112–115.

    D. F. Swaab and E. Fliers (1985)

  39. 35. Two sexually dimorphic cell groups in the human brain. Journal of Neuroscience 9: 497–506.

    Laura S. Allen, Melissa Hines, James E. Shryne, and Roger A. Gorski (1989)

  40. 36. Effects of discrete lesions of the sexually dimorphic nucleus of the preoptic area or other medial preoptic regions on the sexual behavior of male rats. Brain Research Bulletin 10: 147–154.

    Gary W. Arendash and Roger A. Gorski (1983)

  41. 37. Sexual behavior in male Rhesus monkeys elicited by electrical stimulation of preoptic and hypothalamic areas. Brain Research 177: 127–144.

    A. A. Perachio, L. D. Marr, and M. Alexander (1979)

  42. 38. Medial preoptic and hypothalamic neuronal activity during sexual behavior of the male monkey. Brain Research 266: 340–343.

    Y. Oomura, H. Yoshimatsu, and S. Aou (1983)

  43. 39. Demonstration of a sexual dimorphism in the distribution of serotonin-immunoreactive fibers in the medial preoptic nucleus of the rat. Journal of Comparative Neurology 225: 151–166.

    R. B. Simerly, L. W. Swanson, and R. A. Gorski (1984)

  44. 40. Reversal of the sexually dimorphic distribution of serotoninimmunoreactive fibers in the medial preoptic nucleus by treatment with perinatal androgen. Brain Research 340: 91–98.

    R. B. Simerly, L. W. Swanson, and R. A. Gorski (1985)

  45. 41. Sex differences in vasopressin and other neurotransmitter systems in the brain. Progress in Brain Research 61: 185–197.

    G. J. De Vries, R. M. Buijs, and F. W. van Leeuwen (1984)

  46. III. MECHANISMS OF CREATING DIMORPHISMS Receptor-Mediated Estrogenic Effects
  47. 42. Distribution of androgen target cells in rat forebrain and pituitary after 3H-dihydrotestosterone administration. Journal of Steroid Biochemistry 8: 1131–1135.

    Madhabananda Sar and Walter E. Stumpf (1977)

  48. 43. Developmental changes in estrogen receptors in mouse cerebral cortex between birth and postweaning: Studied by autoradiography with 11b-methoxy-16a-125I iodoestradiol. Endocrinology 126: 1112–1124.

    Paul J. Shughrue, Walter E. Stumpf, Neil J. MacLusky, Jan E. Zielinski, and Richard B. Hochberg (1990)

  49. 44. A previously uncharacterized role for estrogen receptor b: Defeminization of male brain and behavior. Proceedings of the National Academy of Sciences USA 102: 4608–4612.

    Andrea E. Kudwa, Cristian Bodo, Jan-Ake Gustafsson, and Emilie F. Rissman (2005)

  50. 45. ER-X: A novel, plasma membrane-associated, putative estrogen receptor that is regulated during development and after ischemic brain injury. Journal of Neuroscience 22: 8391–8401.

    C. Dominique Toran-Allerand, Xiaoping Guan, Neil J. MacLusky, Tamas L. Horvath, Sabrina Diano, Meharvan Singh, E. Sander Connolly Jr, Imam S. Nethrapalli, and Alexander A. Tinnikov (2002)

  51. 46. Sex steroids and the development of the newborn mouse hypothalamus and preoptic area in vitro: Implications for sexual differentiation. Brain Research 106: 407–412.

    C. Dominique Toran-Allerand (1976)

  52. 47. Sex steroids promote neurite growth in mesencephalic tyrosine hydroxylase immunoreactive neurons in vitro. International Journal of Developmental Neuroscience 5: 91–98.

    Ingrid Reisert, Victor Han, Erich Lieth, Dominique Toran-Allerand, Christoph Pilgrim, and Jean Lauder (1987)

  53. 48. Estrogen receptors colocalize with low-affinity nerve growth factor receptors in cholinergic neurons of the basal forebrain. Proceedings of the National Academy of Sciences USA 89: 4668–4672.

    C. Dominique Toran-Allerand, Rajesh C. Miranda, Wayne D. L. Bentham, Farida Sohrabji, Theodore J. Brown, Richard B. Hochberg, and Neil J. MacLusky (1992)

  54. 49. Early estrogen-induced nuclear changes in rat hypothalamic ventromedial neurons: An ultrastructural and morphometric analysis. Journal of Comparative Neurology 239: 255–266.

    Kathryn J. Jones, Donald W. Pfaff, and Bruce S. McEwen (1985)

  55. 50. 5,7- Dihydroxytryptamine and gonadal steroid manipulation alter spine density in ventromedial hypothalamic neurons. Neuroendocrinology 54: 653–657.

    Maya Frankfurt and Bruce S. McEwen (1991)

  56. 51. Estradiol mediates fluctuation in hippocampal synapse density during the estrous cycle in the adult rat. Journal of Neuroscience 12: 2549–2554.

    Catherine S. Woolley and Bruce S. McEwen (1992)

  57. 52. Sex differences of hypothalamic prolactin cells develop independently of the presence of sex steroids. Brain Research 593: 253–256.

    Cordian Beyer, Walter Kolbinger, Ulrike Froehlich, Christof Pilgrim, and Ingrid Reisert (1992)

  58. 53. A model system for study of sex chromosome effects on sexually dimorphic neural and behavioral traits. Journal of Neuroscience 15: 9005–9014.

    Geert J. De Vries, Emilie F. Rissman, Richard B. Simerly, Liang-Yo Yang, Elka M. Scordalakes, Catherine J. Auger, Amanda Swain, Robin Lovell-Badge, Paul S. Burgoyne, and Arthur P. Arnold (2002)

  59. 54. Steroid hormones and the brain: Linking "nature" and "nurture." Neurochemical Research 13: 663–669.

    Experience Bruce S. McEwen (1988)

  60. 55. Motherhood modifies magnocellular neuronal interrelationships in functionally meaningful ways. In N. A. Krasnegor and R. S. Bridges (Eds.), Mammalian Parenting: Biochemical, Neurobiological, and Behavioral Determinants. New York, Oxford University Press.

    Barbara K. Modney and Glenn I. Hatton (1990)

  61. 56. Alterations of the cortical representation of the rat ventrum induced by nursing behavior. Journal of Neuroscience 14: 1710–1721.

    Christian Xerri, Judith M. Stern J. M., and Michael M. Merzenich (1994)

  62. IV. DIMORPHISMS AND COGNITION Intellectual and Spatial Abilities
  63. 57. Sex-dependent behavioral effects of cerebral cortical lesions in the developing Rhesus monkey. Science 186: 540–542.

    Patricia S. Goldman, Howard T. Crawford, Linton P. Stokes, Thelma W. Galkin, and H. Enger Rosvold (1974)

  64. 58. Sex and the single hemisphere: Specialization of the right hemisphere for spatial processing. Science 193: 425–427.

    Sandra F. Witelson (1976)

  65. 59. Sex differences in the effects of unilateral brain damage on intelligence. Science 212: 693–695.

    James Inglis and J. S. Lawson (1981)

  66. 60. Lefthandedness: Association with immune disease, migraine, and developmental learning disorder. Proceedings of the National Academy of Sciences USA 79: 5097–5100.

    Norman Geschwind and Peter Behan (1982)

  67. 61. Cognitive abilities in androgen-insensitive subjects: Comparison with control males and females from the same kindred. Clinical Endocrinology 34: 341–347.

    Julianne Imperato-McGinley, Marino Pichardo, Teofilo Gautier, Daniel Voyer, and M. Philip Bryden (1991)

  68. 62. Sex differences in regional cerebral glucose metabolism during a resting state. Science 267: 528–531.

    Ruben C. Gur, Lyn Harper Mozley, P. David Mozley, Susan M. Resnick, Joel S. Karp, Abass Alavi, Steven T. Arnold, and Raquel E. Gur (1995)

  69. 63. Sex differences in cerebral organization for speech and praxic functions. Canadian Journal of Psychology 37: 19–35.

    Doreen Kimura (1983)

  70. 64. Women have greater density of neurons in posterior temporal cortex. Journal of Neuroscience 15: 3418–3428.

    S. F. Witelson, I. I. Glezer, and D. L. Kigar (1995)

  71. 65. Sex differences in the functional organization of the brain for language. Nature 373: 607–609.

    Bennett A. Shaywitz, Sally E. Shaywitz, Kenneth R. Pugh, R. Todd Constable, Pawel Skudlarski, Robert K. Fulbright, Richard A. Bronen, Jack M. Fletcher, Donald P. Shankweiler, Leonard Katz, and John C. Gore (1995)

  72. 66. Sex differences in functional brain activation during a lexical visual field task. Brain and Language 80: 97–105.

    Susan L. Rossell, Edward T. Bullmore, Steve C. R. Williams, and Anthony S. David (2002)

  73. 67. Sexual dimorphism in the human corpus callosum. Science 216: 1431–1432.

    Christine de Lacoste-Utamsing and Ralph L. Holloway (1982)

  74. 68. No sex-related differences in human corpus callosum based on magnetic resonance imagery. Annals of Neurology 21: 604–606.

    Jeffrey S. Oppenheim, Benjamin C. P. Lee, Ruth Nass, and Michael S. Gazzaniga (1987)

  75. 69. Sexual dimorphism of the human corpus callosum from three independent samples: Relative size of the corpus callosum. American Journal of Physical Anthropology 92: 481–498.

    Ralph L. Halloway, Paul J. Anderson, Richard Defendini, and Clive Harper (1993)

  76. 70. Sexual dimorphism of the anterior commissure and massa intermedia of the human brain. Journal of Comparative Neurology 312: 97–104.

    Laura S. Allen and Roger A. Gorski (1991)

  77. 71. Sex differences in the corpus callosum of the living human being. Journal of Neuroscience 11: 933–942.

    Laura S. Allen, Mark F. Richey, Yee M. Chai, and Roger A. Gorski (1991)

  78. 72. Disruption of estrogen receptor b gene impairs spatial learning in female mice. Proceedings of the National Academy of Sciences USA 99: 3996–4001.

    Emilie F. Rissman, Amy L. Heck, Julie E. Leonard, Margaret A. Shupnik, and Jan-Ake Gustafsson (2002)

  79. 73. Spatial memory performance in androgen insensitive male rats. Physiology and Behavior 85: 135–141.

    Bryan A. Jones and Neil V. Watson (2005)

  80. V. DIMORPHISMS AND IDENTITY
  81. 74. Androgens and gender role behaviour in girls with congenital adrenal hyperplasia. Progress in Brain Research 61: 417–422.

    Froukje M. E. Slijper (1984)

  82. 75. Gender dysphoria and gender change in androgen insensitivity or micropenis. Archives of Sexual Behavior 34: 411–421.

    Tom Mazur (2005)

  83. 76. Correlation between genotype, phenotype, and sex of rearing in 111 patients with partial androgen insensitivity syndrome. Clinical Endocrinology 63: 56–62.

    A. Deeb, C. Mason, Y. S. Lee, and I. A. Hughes (2005)

  84. 77. Heterosexual, autosexual and social behavior of adult male Rhesus monkeys with medial preoptic-anterior hypothalamic lesions. Brain Research 142: 105–122.

    Jefferson C. Slimp, Benjamin L. Hart, and Robert W. Goy (1978)

  85. 78. Sexual orientation after prenatal exposure to exogenous estrogens. Archives of Sexual Behavior 14: 57–77.

    Anke A. Ehrhardt, Heino F. L. Meyer-Bahlburg, Laura R. Rosen, Judith F. Feldman, Norma P. Veridiano, I. Zimmerman, and Bruce S. McEwen (1985)

  86. 79. An enlarged suprachiasmatic nucleus in homosexual men. Brain Research 537: 141–148.

    D. F. Swaab and M. A. Hofman (1990)

  87. 80. A difference in hypothalamic structure between heterosexual and homosexual men. Science 253: 1034–1037.

    Simon LeVay (1991)

  88. 81. Sexual orientation and the size of the anterior commissure in the human brain. Proceedings of the National Academy of Sciences USA 89: 7199–7202.

    Laura S. Allen and Roger A. Gorski (1992)

  89. 82. Brain response to putative pheromones in homosexual men. Proceedings of the National Academy of Sciences USA 102: 7356–7361.

    Ivanka Savic, Hans Berglund, and Per Lindstrom (2005)

  90. Transgendered and Gendered sexual disorders in children and adolescents. Child Psychology and Psychiatry 33: 107–151.

    Kenneth J. Zucker and Richard Green (1992)

  91. 84. Estrogen positive feedback on LH secretion in transsexuality. Psychoneuroendocrinology 9: 249–259.

    L. J. G. Gooren, B. R. Rao, H. van Kessel, and W. Harmsen-Louman (1984)

  92. 85. A sex difference in the human brain and its relation to transsexuality. Nature 378: 68–70.

    Jiang-Ning Zhou, Michel A. Hofman, Louis J. G. Gooren, and Dick F. Swaab (1995)

  93. 86. Male-to-female transsexuals have female neuron numbers in a limbic nucleus. Journal of Clinical Endocrinology and Metabolism 85: 2034–2041.

    Frank P. M. Kruijver, Jiang-Ning Zhou, Chris W. Pool, Michel A. Hofman, Louis J. G. Gooren, and Dick F. Swaab (2000)

  94. Epilog
  95. 87. Review: Historical origins of modern research on hormones and behavior. Hormones and Behavior 15: 325–376.

    Frank A. Beach (1981)

  96. Index