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Vol. 50, No. 5, 1998
Issue release date: November 1998

Sexual Differentiation: From Genes to Gender

Migeon C.J. · Wisniewski A.B.
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A person’s sex can be considered across various levels. To illustrate, genes, hormones, and genitalia can all be considered physical markers of a person’s sex. In addition to physical markers, behaviors such as gender role, gender identity and sexual orientation can be perceived as stereotypically male or female. The purpose of this review is to summarize current knowledge of sexual differentiation which emphasizes genetic and hormonal mechanisms that result in male and female development of gonads and genitalia. Finally, consideration is given to associations between genetic sex, gonadal sex, and hormonal sex with gender.

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  1. Stedman’s Medical Dictionary, ed 24. Baltimore, Williams & Wilkins, 1982.
  2. Ford CE, Hamerton JL: The chromosomes of man. Nature 1956;178:1020.
  3. Tijo JH, Levan A: The chromosomal number of man. Hereditas 1956;42:1.
  4. Langman L: Medical Embryology, ed 2. Baltimore, Williams & Wilkins, 1969.
  5. Jirasek JE: Development of the genital system and male pseudohermaphroditism; in Cohen MM (ed): Baltimore, Johns Hopkins Press, 1971.
  6. Jirasek JE: Morphogenesis of the genital system in the human; in Blandau RJ, Bergsma D (eds): Birth Defects: Original Article Series. New York, Liss, 1977, vol 13, p 13.
  7. Witschi E: Migration of germ cells of human embryos from the yolk sac to the primitive gonadal folds. Contrib Embryol 1948;32:67.
  8. Josso N: Physiology of sex differentiation. A guide to the understanding and management of the intersex child; in Josso N (ed): The Intersex Child. Basel, Karger, 1981, pp 1–13.
  9. Magre S, Jost A: Dissociation between testicular organogenesis and endocrine cytodifferentiation of Sertoli cells. Proc Natl Acad Sci USA 1984;81:7831.

    External Resources

  10. Pelliniemi LJ, Niemi M: Fine structure of the human foetal testis. I. The interstitial tissue. Z Zellforsch 1969;99:507.
  11. Siiteri PK, Wilson JD: Testosterone formation and metabolism during male sexual differentiation in the human embryo. J Clin Endocrinol Metab 1974;38:113.

    External Resources

  12. McLaren A: Somatic and germ-cell sex in mammals. Philos Trans R Soc Lond B Biol Sci 1988;322:3–9.

    External Resources

  13. Byskov AG: Differentiation of mammalian embryonic gonad. Physiol Rev 1986;66:71–117.
  14. Jost A, Magre S: Control mechanisms of testicular differentiation. Philos Trans R Soc Lond B Biol Sci 1988;322:55–61.

    External Resources

  15. MacLean HE, Warne GL, Zajac JD: Intersex disorders: Shedding light on male sexual differentiation beyond SRY. Clin Endocrinol 1997;46:101.
  16. Sinclair AH, Berta P, Palmer MS, Hawkins JR, Griffiths BLM, Smith J, Foster JW, Frischauf A, Lovell-Badge R, Goodfellow PN: A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif. Nature 1990;346:240.
  17. Fechner PY: The role of SRY in mammalian sex determination. Acta Paediatr Jpn 1996;38:380.
  18. Smith MJ: Turning on sex. Curr Biol 1994;4:10.
  19. Shen W, Moore CCD, Ikeda Y, Parker KL, Ingraham HA: Nuclear receptor steroidogenic factor 1 regulates the mullerian inhibiting substance gebe: A link to the sex determination cascade. Cell 1994;77:651.
  20. McElreavey K, Barbaux S, Ion A, Fellous M: The genetic basis of murine and human sex determination. Heredity 1995;75:599.
  21. Berkovitz GD, Fechner PY, Marcantonio SM, Bland G, Stetten G, Goodfellow PN, Smith KD, Migeon CJ: The role of the sex-determining region of the Y chromosome (SRY) in the etiology of 46,XX true hermaphroditism. Hum Genet 1992;88:411.
  22. Fechner PY, Marcantonio SM, Jaswaney V, Stetten G, Goodfellow PN, Migeon CJ, Smith KD, Berkovitz GD: The role of the sex determining region Y gene in the etiology of 46,XX maleness. J Clin Endocrinol Metab 1993;76:690.
  23. Ogata T, Matsuo N: Testis determining gene(s) on the X chromosome short arm: Chromosomal localization and possible role in testis determination. J Med Genet 1994;31:349.
  24. Bardoni B, Zanaria E, Guiolo S, Floridia G, Worley K, Tonini G, Ferrante E, Chiumello G, McCabe ERB, Fraccaro M, Zuffardi O, Camerino G: A dosage sensitive locus at chromosome Xp21 is involved in male to female sex reversal. Nat Genet 1994;7:497.
  25. Swain A, Narvaez V, Burgoyne P, Camerino G, Lovell-Badge R: Dax1 antagonizes Sry action in mammalian sex determination. Nature 1998;391:761.
  26. George FW, Wilson JD: Conversion of androgen to estrogen by human fetal ovary. J Clin Endocrinol Metab 1978;47:550.

    External Resources

  27. Luo X, Ikeda Y, Parker KL: A cell-specific nuclear receptor is essential for adrenal and gonadal development and sexual differentiation. Cell 1994;77:481.
  28. Burris TP, Guo W, Le T, McCabe ERB: Identification of a putative steroidogenic factor-1 response element in the DAX-1 promoter. Biochem Biophys Res Commun 1995;214:576.
  29. Josso N: Hormonal regulation of sexual differentiation. Semin Perinatol 1992;16:274.
  30. Huhtaniemi I: Fetal testis – A very special endocrine organ. Eur J Endocrinol 1994;130:25.
  31. Tapanainen J, Kellokumpu-Lehtinen P, Pelliniemi L, Huhtaniemi I: Age-related changes in endogenous steroids of human fetal testis during early and midpregnancy. J Clin Endocrinol Metab 1981;52:98.

    External Resources

  32. Price T, Aitken J, Simpson ER: Relative expression of aromatase cytochrome P450 in human fetal tissue as determined by competitive polymerase chain reaction amplification. J Clin Endocrinol Metab 1992;74:879.

    External Resources

  33. Brown TR, Migeon CJ: Cultured human skin fibroblasts for the study of androgen action. Mol Cell Biochem 1981;36:3.

    External Resources

  34. Swaab DF, Gooren LJG, Hofman MA: Gender and sexual orientation in relation to hypothalamic structures. Horm Res 1992;38:51.
  35. Zucker KJ, Bradley SJ: Gender Identity Disorder and Psychosexual Problems in Children and Adolescents. New York, Guilford Press, 1995.
  36. Money J: Biographies of Gender and Hermaphroditism in Paired Comparisons. New York, Elsevier, 1991.
  37. Mulaikal RM, Migeon CJ, Rock JA: Fertility rates in female patients with congenital adrenal hyperplasia dueto 21-hydroxylase deficiency. N Engl Med 1987;316:178.

    External Resources

  38. Dittmann RW, Kappes MH, Kappes ME, Borger D, Meyer-Bahlburg HFL, Stegner H, Willig RH, Wallis H: Congenital adrenal hyperplasia. II. Gender-related behavior and attitudes in female salt-wasting and simple-virilizing patients. Psychoneuroendocrinology 1990;15:421–434.
  39. Money J, Schwartz M, Lewis VC: Adult erotosexual status and fetal hormonal masculinization: 46,XX congenital virilizing adrenal hyperplasia and 46,XY androgen insensitivity syndrome compared. Psychoneuroendocrinology 1984;9:405.
  40. Migeon CJ, Brown TR, Fichman KR: Androgen insensitivity syndrome; in Josso N (ed): Pediatric and Adolescent Endocrinology: The Intersex Child. Basel, Karger, 1981, vol 8, p 171.
  41. Diamond M, Sigmundson K: Sex reassignment at birth: Long-term review and clinical implications. Arch Pediatr Adolesc Med 1997;151:298–304.
  42. Bradley SJ, Oliver GD, Chernick AB, Zucker KJ: Experiment of nature: Ablatio penis at 2 months, sex reassignment at 7 months, and a psychosexual follow-up in young adulthood. Pediatrics 1998;102:e9.

    External Resources

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