DNA Basics

If a person has a total gender reassignment - (sex change) no matter how extreme the operation goes with hormone injections etc; on a DNA level, the sex of that person is absolute?

-A curious adult from Singapore

July 23, 2004

No amount of surgery, hormone injections or anything else will change someone's DNA from a man's to a woman's (or vice versa).

As you know, for humans, sex is determined by the presence of a Y chromosome -- humans with an X and a Y chromosome are male and those with two X chromosomes are female. No current (or probably future) technology can replace a chromosome in all of our trillions of cells.

In fact, it probably wouldn't matter if they did. The genes on the Y chromosome sort of get the ball rolling for becoming a male. Once that has happened, the system can go on indefinitely.

How does the Y chromosome make someone a male? There is a gene called SRY on the Y chromosome that allows certain genes to be turned. Once on, these genes cause testes to form instead of ovaries.

Once the testes form, they make lots of testosterone. As you know, testosterone is the "male hormone." However, testosterone by itself can do nothing -- it needs a protein called the androgen receptor to have any effect. Like testosterone, the androgen receptor by itself can't do anything either.

When the androgen receptor and testosterone get together, they turn on lots of genes. In the womb, these genes cause male plumbing to develop. At puberty, the genes that are turned on cause you to get a deeper voice, more body hair and muscle mass, make sperm, etc.

As you stated in your question, in a sex change operation, the patient is given hormone injections. In a female to male change, they are given testosterone injections. The reason this works is that women have lots of androgen receptors. In fact the gene for the androgen receptor is found on the X chromosome.

Why would women have any androgen receptors lying around? Women have the androgen receptor because their ovaries and adrenal glands make testosterone. They just don't make enough to turn on the genes needed for a deep voice, etc. -- women have about 10 times less testosterone than do men*.

So as you can see, with a sex change operation the underlying DNA stays whatever sex they started out with. The hormone injections, though, cause a different set of genes on the DNA to be turned on so that you get, for example, a male pattern of gene expression in someone who is XX.

*The situation is similar in a male to female change. The hormone is estrogen and the receptor is called the estrogen receptor. Both men and women have the estrogen receptor which can be found on chromosome 6.

By Dr. Barry Starr, Stanford University