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19 October 2007
New Method Of Gender Assignment For Intersex Conditions
by George Atkinson

The discovery of a stable sex hormone "signature" in human cells could soon help in assigning gender to intersex individuals whose genitals and sex chromosomes don't match. Published in the journal BMC Genomics, the new study shows for the first time that testosterone leaves an irreversible molecular "signature" in cells that may provide a much more accurate way to look at sex than just ascertaining the presence of the Y chromosome.

US and German researchers were able to pinpoint the role of testosterone by comparing individuals with complete androgen insensitivity syndrome (CAIS) to people without CAIS. The findings provide a foundation that may lead to improved treatments for those whose gender is ambiguous (known as intersex condition).

"Androgens have long lasting effects during certain sensitive stages of our genital development and this is probably true for other organs," explained lead researcher Paul-Martin Holterhus. "It is currently increasingly accepted that the brain shows sex-specific development in response to presence or absence of testosterone. This affects sex specific behavior and probably modulates gender identity."

The role of androgens (especially testosterone) in sexual development has long been known. Gender programming begins in the embryo and is thought to continue throughout life, particularly during puberty. However, what is not understood are the different roles of sex chromosome genes versus the long-term programming effects of sex hormones, namely androgens.

CAIS affects 1 in 20,000 people. While they look like normal females, at a genetic level CAIS women have XY sex chromosomes rather than the usual XX.

The condition is due to mutations in the gene coding for the androgen receptor, which means that androgen signaling doesn't work: it essentially knocks out the effect of testosterone. The researchers used skin biopsies of external genitalia to compare the gene expression of normal males and CAIS females. Analysis revealed that between males and females, 440 genes differed in their level of transcription. The activity levels of these genes form a 'signature' that could be developed to help understand more about individual AIS cases.

"Since we compared XY females with the XY males, the difference can only be explained by differences in androgen action and not by differences in sex chromosomes," explained Holterhus. "Another intriguing observation is that the one normal female [with a 46,XX genotype] in our study did not differ a lot with respect to the identified genes from the XY females. This is an important reassurance for XY females because it limits the role of the sex chromosomes in gender assignment."

Related articles:
XYY - One Chromosome Too Many
Intersex - The Third Gender
Orgasm Problems Common With Intersex Conditions
Ambiguous Genitalia Babies Mostly Happy With Gender Assignment
Delay Gender Reassignment, Say Surgeons

Source: BioMed Central




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