Best Practice & Research Clinical Endocrinology & Metabolism
Volume 21, Issue 3 , Pages 431-444 , September 2007

Sexual differentiation of the brain and behavior

  • Dick F. Swaab (Professor)

      Affiliations

    • Corresponding Author InformationTel.: +31 20 5665500; Fax: +31 20 6961006.

References 

  1. Swaab DF. The Human Hypothalamus. Basic and Clinical Aspects. Part II: Neuropathology of the Hypothalamus and Adjacent Brain Structures. In:  Aminoff MJ,  Boller F,  Swaab DF editor. Handbook of Clinical Neurology. Amsterdam: Elsevier; 2004;596 pp.
  2. Bakker J, De Mees C, Douhard Q, et al. Alpha-fetoprotein protects the developing female mouse brain from masculinization and defeminization by estrogens. Nature Neuroscience. 2006;9:220–226
  3. Gorski RA. Critical role for the medial preoptic area in the sexual differentiation of the brain. Progress in Brain Research. 1984;61:129–146
  4. Mayer A, Swaab DF, Pilgrim C. Genes involved in male sex determination are expressed in adult human brain. Neurogenetics. 1998;1:281–288
  5. Dewing P, Shi T, Horvath S, Vilain E. Sexually dimorphic gene expression in mouse brain precedes gonadal differentiation. Brain Research. Molecular Brain Research. 2003;118:82–90
  6. Lopes AM, Ross N, Close J, et al. Inactivation status of PCDH11X: sexual dimorphisms in gene expression levels in brain. Human Genetics. 2006;119:267–275
  7. Finegan JA, Bartleman B, Wong PY. A window for the study of prenatal sex hormone influences on postnatal development. The Journal of General Psychology. 1989;150:101–112
  8. De Zegher F, Devlieger H, Veldhuis JD. Pulsatile and sexually dimorphic secretion of luteinizing hormone in the human infant on the day of birth. Pediatric research. 1992;32:605–607
  9. Quigley CA. The postnatal gonadotropin and sex steroid surge—insights from the androgen insensitivity syndrome. The Journal of Clinical Endocrinology and Metabolism. 2002;87:24–28
  10. Money J. Ablatio penis: normal male infant sex-reassigned as a girl. Archives of Sexual Behavior. 1975;4:65–71
  11. Colapinto J. As Nature Made Him. The Boy Who was Raised as a Girl. New York: Harper Collins Publishers Inc; 2001;
  12. Alexander GM, Hines M. Sex differences in response to children's toys in nonhuman primates (Cercopithecus aethiops sabaeus). Evolution and Human Behavior. 2002;23:467–479
  13. Nordenström A, Servin A, Bohlin G, et al. Sex-typed toy play behavior correlates with the degree of prenatal androgen exposure assessed by CYP21 genotype in girls with congenital adrenal hyperplasia. The Journal of Clinical Endocrinology and Metabolism. 2002;87:5119–5124
  14. Iijima M, Arisaka O, Minamoto F. Sex differences in children's free drawings: a study on girls with congenital adrenal hyperplasia. Hormones and Behavior. 2001;40:90–104
  15. Money J, Erhardt AA. Man and Woman, Boy and Girl: The Differentiation and Dimorphism of Gender Identity from Conception to Maturity. Baltimore: Johns Hopkins University Press; 1972;
  16. Diamond M, Sigmundson K. Sex reassignment at birth. Long-term review and clinical implications. Archives of Pediatrics & Adolescent Medicine. 1997;151:298–304
  17. LeVay S. Queer Science. The Use and Abuse of Research into Homosexuality. Cambridge, MA, USA: The MIT Press; 1996;
  18. Miller BL, Cummings JL, McIntyre H, et al. Hypersexuality or altered sexual preference following brain injury. Journal of Neurology, Neurosurgery, and Psychiatry. 1986;49:867–873
  19. Burns JM, Swerdlow RH. Right orbitofrontal tumor with pedophilia symptom and constructional apraxia sign. Archives of Neurology. 2003;60:437–440
  20. Dieckmann G, Hassler R. Treatment of Sexual Violence by Stereotactic Hypothalamotomy. In:  Sweet WH,  Obrador S,  Martin-Rodriguez JG editor. Neurosurgical Treatment in Psychiatry, Pain, and Epilepsy. Baltimore: Univ Park Press; 1977;p. 451–462
  21. Spitzer RL. Can some gay men and lesbians change their sexual orientation? 200 Participants reporting a change from homosexual to heterosexual orientation. Archives of Sexual Behavior. 2003;32:403–417
  22. Wisniewski AB, Migeon CJ, Meyer-Bahlburg HFL, et al. Complete androgen insensitivity syndrome: long-term medical, surgical, and psychosexual outcome. The Journal of Clinical Endocrinology and Metabolism. 2000;85:2664–2669
  23. Wilson JD, Griffin JE, Russell DW. Steroid 5a-reductase 2 deficiency. Endocrine Reviews. 1993;14:577–593
  24. Hughes IA, Houk C, Ahmed SF, et al. Consensus statement on management of intersex disorders. Archives of Diseases Childhood. 2006;91:554–563
  25. Imperato-McGinley J, Peterson RE, Gautier T. Male pseudohermaphroditism secondary to 5α-reductase deficiency—a model for the role of androgens in both the development of the male phenotype and the evolution of a male gender identity. Journal of Steroid Biochemistry. 1979;11(1B):637–645
  26. Cohen-Kettenis PT. Gender change in 46,XY persons with 5α-reductase-2 deficiency and 17β-hydroxysteroid dehydrogenase-3 deficiency. Archives of Sexual Behavior. 2005;34:399–410
  27. Meyer-Bahlburg HFL. Gender identity outcome in female-raised 46,XY persons with penile agenesis, cloacal exstrophy of the bladder, or penile ablation. Archives of Sexual Behavior. 2005;34:423–438
  28. Reiner WG, Gearhart JP. Discordant sexual identity in some genetic males with cloacal exstrophy assigned to female sex at birth. The New England Journal of Medicine. 2004;350:333–341
  29. Cohen-Kettenis PT, Gooren LJG. Transsexualism: a review of etiology, diagnosis and treatment. Journal of Psychosomatic Research. 1998;46:315–333
  30. Coolidge FL, Thede LL, Young SE. The heritability of gender identity disorder in a child and adolescent twin sample. Behavior Genetics. 2002;32:251–257
  31. Henningsson S, Westberg L, Nilsson S, et al. Sex steroid-related genes and male-to-female transsexualism. Psychoneuroendocrinology. 2005;30:657–664
  32. Padmanabhan V, Manikkam M, Recabarren S, et al. Prenatal testosterone excess programs reproductive and metabolic dysfunction in the female. Molecular and Cellular Endocrinology. 2005;246:165–174
  33. Zucker KJ, Bradley SJ, Oliver G, et al. Psychosexual development of women with congenital adrenal hyperplasia. Hormones and Behavior. 1996;30:300–318
  34. Dessens AB, Slijper FM, Drop SL. Gender dysphoria and gender change in chromosomal females with congenital adrenal hyperplasia. Archives of Sexual Behavior. 2005;34:389–397Review
  35. Dessens AB, Cohen-Kettenis PT, Mellenbergh GJ, et al. Prenatal exposure to anticonvulsants and psychosexual development. Archives of Sexual Behavior. 1999;28:31–44
  36. Kerlin, DES Action USA; DES Sons' information page. http://www.desaction.org/sons.htm2005;
  37. Zhou JN, Hofman MA, Gooren LJG, et al. A sex difference in the human brain and its relation to transsexuality. Nature. 1995;378:68–70
  38. Kruijver FPM, Zhou JN, Pool CW, et al. Male-to-female transsexuals have female neuron numbers in a limbic nucleus. The Journal of Clinical Endocrinology and Metabolism. 2000;85:2034–2041
  39. Chung WC, De Vries GJ, Swaab DF. Sexual differentiation of the bed nucleus of the stria terminalis in humans may extend into adulthood. The Journal of Neuroscience. 2002;22:1027–1033
  40. LeVay S, Hamer DH. Evidence for a biological influence in male homosexuality. Scientific American. 1994;270:44–49
  41. Camperio-Ciani A, Corna F, Capiluppi C. Evidence for maternally inherited factors favouring male homosexuality and promoting female fecundity. Proceedings. Biological Sciences. 2004;271:2217–2221
  42. Meyer-Bahlburg HFL, Gruen RS, New MI. Gender change from female to male in classical congenital adrenal hyperplasia. Hormones and Behavior. 1996;30:319–332
  43. Ehrhardt AA, Meyer-Bahlburg HFL, Rosen LR. Sexual orientation after prenatal exposure to exogenous estrogen. Archives of Sexual Behavior. 1985;14:57–75
  44. Meyer-Bahlburg HFL, Ehrhardt AA, Rosen LR. Prenatal estrogens and the development of homosexual orientation. Developmental Psychology. 1995;31:12–21
  45. Titus-Ernstoff L, Perez K, Hatch EE, et al. Psychosexual characteristics of men and women exposed prenatally to diethylstilbestrol. Epidemiology. 2003;14:155–160
  46. Blanchard R. Fraternal birth order and the maternal immune hypothesis of male homosexuality. Hormones and Behavior. 2001;40:105–114
  47. Bogaert AF. The interaction of fraternal birth order and body size in male sexual orientation. Behavioral Neuroscience. 2003;117:381–384
  48. Ellis L, Cole-Harding S. The effects of prenatal stress, and of prenatal alcohol and nicotine exposure, on human sexual orientation. Physiology & Behavior. 2001;74:213–226
  49. Ellis L, Hellberg J. Fetal exposure to prescription drugs and adult sexual orientation. Personality and Individual Differences. 2005;38:225–236
  50. Ellis L, Ames MA, Peckham W, et al. Sexual orientation of human offspring may be altered by severe maternal stress during pregnancy. Journal of Sex Research. 1988;25:152–157
  51. Bailey JM, Willerman L, Parks C. A test of the maternal stress theory of human male homosexuality. Archives of Sexual Behavior. 1991;20:277–293
  52. Green R. Sexual identity of 37 children raised by homosexual or transsexual parents. The American Journal of Psychiatry. 1978;135:692–697
  53. Swaab DF. The Human Hypothalamus. Basic and Clinical Aspects. Part I: Nuclei of the Hypothalamus. In:  Aminoff MJ,  Boller F,  Swaab DF editor. Handbook of Clinical Neurology. Amsterdam: Elsevier; 2003;476 pp.
  54. Swaab DF, Hofman MA. An enlarged suprachiasmatic nucleus in homosexual men. Brain Research. 1990;537:141–148
  55. Swaab DF, Slob AK, Houtsmuller EJ, et al. Increased number of vasopressin neurons in the suprachiasmatic nucleus (SCN) of ‘bisexual’ adult male rats following perinatal treatment with the aromatase blocker ATD. Brain Research. Developmental Brain Research. 1995;85:273–279
  56. LeVay S. A difference in hypothalamic structure between heterosexual and homosexual men. Science. 1991;253:1034–1037
  57. Allen LS, Gorski RA. Sexual orientation and the size of the anterior commissure in the human brain. Proceedings of theNational Academy of Sciences of the United States of America. 1992;89:7199–7202
  58. Kinnunen LH, Moltz H, Metz J, Cooper M. Differential brain activation in exclusively homosexual and heterosexual men produced by the selective serotonin reuptake inhibitor, fluoxetine. Brain Research. 2004;1024:251–254
  59. Savic I, Berglund H, Lindstrom P. Brain response to putative pheromones in homosexual men. Proceedings of the National Academy of Sciences of the United States of America. 2005;102:7356–7361
  60. Berglund H, Lindström P, Savic I. Brain response to putative pheromones in lesbian women. Proceedings of the National Academy of Sciences of the United States of America. 2006;103:8269–8274
  61. Kranz F, Ishai A. Face perception is modulated by sexual preference. Current Biology. 2006;16:63–68
  62. Bailey JM, Bell AP. Familiality of female and male homosexuality. Behavior Genetics. 1993;23:313–322

PII: S1521-690X(07)00033-4

doi: 10.1016/j.beem.2007.04.003

Best Practice & Research Clinical Endocrinology & Metabolism
Volume 21, Issue 3 , Pages 431-444 , September 2007