Androgen Insensitivity Syndrome

AIS can best be understood against the background of normal human sexual development, which begins in the womb. The gonads arise from the same embryonic tissue, which is differentiated into one or the other by the actions of several genes not involved in AIS. In males, the most important gene is SRY, located on the Y chromosome. When present, this causes testis development. The genes responsible for ovary development are not as well characterized.

Once differentiated, the ovaries produce estrogen, and testes produce testosterone. These two hormones provide crucial signals for the differentiation of other sex-related characteristics, including an important set of primitive ducts.

The tubes and cavities that will house the adult's eggs or sperm after they leave the gonads develop from two different sets of ducts. Early in development, every fetus has both sets of ducts. One set, called the Wolffian ducts, has the capacity to develop into the male vas deferens and accessory Normal sexual development is governed by presence or absense of testosterone and AMH. In males, degeneration of the Mullerian ducts is triggered by AMH. Development of the Wolffian ducts is triggered by testosterone. In individuals with androgen insensitivity syndrome, AMH acts but testosterone does not. structures, which store, nourish, and ejaculate sperm. The other set, called the Müllerian ducts, has the capacity to become the female fallopian tubes, uterus, cervix, and upper vagina.

In males, testosterone from the testes stimulates the development of the Wolffian ducts. Testosterone also stimulates nearby tissue to swell and form the penis and scrotum. A second hormone made by the testes, called antiMüllerian hormone (AMH), induces the Müllerian ducts to undergo apoptosis, causing them to degenerate. During puberty, testosterone stimulates the development of other male secondary sex characteristics, including facial hair and a deepening of the voice.

In females, the absence of testosterone and AMH causes the Müllerian ducts to develop and the Wolffian ducts to degenerate. The same tissue that forms the penis and scrotum in males forms the clitoris, labia, and lower vagina in females. At puberty, estrogen stimulates development of female secondary sex characteristics, including enlargement of the breasts and onset of menstruation.