Exactly what causes this variation is not entirely understood, although factors contributing to it could include the lengths of the polyglutamine and polyglycine tracts, sensitivity to and variations in the intrauterine endocrine milieu, the effect of coregulatory proteins active in Sertoli cells, somatic mosaicism, expression of the 5RD2 gene in genital skin fibroblasts, reduced AR transcription and translation from factors other than mutations in the AR coding region, an unidentified coactivator protein, enzyme deficiencies such as 21-hydroxylase deficiency, or other genetic variations such as a mutant steroidogenic factor-1 protein. The degree of variation, however, does not appear to be constant across all AR mutations, and is much more extreme in some. Missense mutations that result in a single amino acid substitution are known to produce the most phenotypic diversity. Pathophysiology
Androgens and the androgen receptor
The effects that androgens have on the human body (virilization, masculinization, anabolism, etc.) are not brought about by androgens themselves, but rather are the result of androgens bound to androgen receptors; the androgen receptor mediates the effects of androgens in the human body.
Society and culture
In the film Orchids, My Intersex Adventure, Phoebe Hart and her sister Bonnie Hart, both women with CAIS, documented their exploration of AIS and other intersex issues.Recording artist Dalea is a Hispanic-American Activist who is public about her CAIS. She has given interviews about her condition and founded Girl Comet, a non-profit diversity awareness and inspiration initiative.In 2017, fashion model Hanne Gaby Odiele disclosed that they were born with the intersex trait androgen insensitivity syndrome. As a child, they underwent medical procedures relating to the condition, which they said took place without their or their parents informed consent. They were told about their intersex condition weeks before beginning their modelling career.In the 1991 Japanese horror novel Ring and its sequels, by Koji Suzuki (later adapted into Japanese, Korean, and American films), the central antagonist Sadako has this syndrome, as revealed by Dr Nagao when confronted by Ryuji and Asakawa. Sadakos condition is referred to by the earlier name "testicular feminisation syndrome". In season 2, episode 13 ("Skin Deep") of the TV series House, the main patients cancerous testicle is mistaken for an ovary due to the patients undiscovered CAIS.In season 2 of the MTV series Faking It, a character has CAIS.