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Sex and the Y Chromosome
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Intersex

For some individuals, determination of biological sex can be difficult. Intersex refers to genetically determined differences of the reproductive system. This can include differences in internal reproductive organs, external genitalia, or karyotype. Mild intersex conditions include, in males, a condition in which the urethra opens on the underside of the penis or, in females, an enlarged clitoris. Female intersexuals (karyotype 46XX) (also called female pseudohermaphrodites) have normal ovarian tissue, and have either male or ambiguous genitalia. This is usually a result of a change in the fetal adrenal glands, leading to production of abnormally high levels of androgens. The androgens produce some masculine features in female infants: ovaries and uterus form, but the external genitalia appear male-like. This accounts for about two-thirds of intersex states.

Male intersexuals (karyotype 46XY) (also called male pseudohermaphrodites) have normal testes with female or ambiguous genitalia. They most often result from several different genetic alterations in pathways of testosterone synthesis and metabolism. For example, males who have a mutation in the gene that converts testosterone to dihydroxytestosterone have normal testes but have a very small penis and a vaginal pouch. In gonadal dysgenesis the testes fail to secrete androgens or Müllerian-inhibiting hormone, leading to formation of female genitalia. With estrogen treatment, however, these individuals will grow into females. A condition called micropenis results from lack of androgens later in fetal life; testosterone treatment can stimulate masculizing puberty in these individuals.

Androgen insensitivity syndrome (AIS) occurs when a male produces cells that cannot respond to androgen. The defect is in a gene on the X chromosome that produces the androgen receptor. Individuals may have complete or partial androgen insensitivity. In complete AIS the testes develop in the embryo, and produce testosterone and the hormone that inhibits development of female internal reproductive organs (Fig. 4). However, because the cells do not respond to testosterone, female genitals develop, which may be incomplete. The newborn appears to be a female and develops external female characteristics at puberty. Lacking internal female reproductive organs, though, the individual with AIS does not menstruate and is infertile. In incomplete AIS, individuals may appear male or female, but there may be abnormalities in the external genitalia. Maria Patino, a Spanish runner with complete AIS, was not allowed to compete in the 1985 World University Games in Kobe, Japan because she failed the gender test. (See the Sex and Gender video.) Because of such difficulties in determining sex, the International Olympic Committee abolished gender testing in 1999.

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