Question about how women can get PFS if the androgen receptor is the root cause

Science PFS Research
#1

I have been reading about the rare genetic disease called Androgen Insensitivity Syndrome (AIS). From what I have read, it only effects males. Women may carry the faulty gene but don’t develop serious phenotypical abnormalities.

AIS patients have dysfunctional androgen receptors. If faulty androgen receptors are also the cause of PFS, how can women be effected by the condition?

See relevant information about AIS below:

Androgen insensitivity syndrome (AIS) is a difference in sex development involving hormonal resistance due to androgen receptor dysfunction.

It affects 1 in 20,000 to 64,000 XY (karyotypically male) births. The condition results in the partial or complete inability of cells to respond to androgens. This unresponsiveness can impair or prevent the development of male genitals, as well as impairing or preventing the development of male secondary sexual characteristics at puberty. It does not significantly impair female genital or sexual development. The insensitivity to androgens is therefore clinically significant only when it occurs in genetic males, (i.e. individuals with a Y-chromosome, or more specifically, an SRY gene).

#2

I’m wondering if we should all just get tested for this it would make sense why testosterone and other androgens don’t work for us, and technically speaking there is no cure for AIS either so it would be interesting to see the results of a study like that done on PFS patients.

#3

The androgen receptor gene is located on the X chromosome, which means women have two AR genes compared to one for males. Plainly speaking, if a female receives one mutated AR gene they have a backup, while a male is screwed.

It is extremely unlikely for a female to receive two mutated AR genes.

That explains why males get AIS (at least the variants based on mutations of the AR), while females don’t. This is inherited.

PFS is likely driven by epigenetic changes of the AR via androgen deprivation. It is not inherited (at least not in its original form) and can affect anyone with ARs, male or female.

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#4

First, It have been such a great work to initiate the charity, the fundraise and the Kiel Study with an Humangenetik research institute, who already released in The Cell and Nature.

For me really new too, that women have two x chromosom located AR genes. But women and men have the entire hormone panel and it seems to be the regulation what decides to develop the correct XX or XY phenotype. And recognizing our own bodies it’s a dynamic livelong process.

#5

That’s what I would have guessed at first but I can’t find scientific literature to confirm this. Are there any cases in the world of a woman with two mutant AR genes? Also, couldn’t scientists genetically engineer female mice to have AIS by altering the AR gene on both of their X chromosomes?

#7

Awor was tested a long time ago with genetic testing and even live time androgen binding to androgen receptor testing (or something like that). It’s been concluded it’s not this for awhile

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#8

What’s more interesting in my opinion is how people gotten “PFS” or PAIS from aromatase inhibitors. FWIW they’re not anti androgens.

However there seems to be slight differences in the symptoms so it might be a similar disease driven from the estrogen receptors (which is what the theory is afaik).

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#9

Yeah this is the thread about it.

Awor and his scientists predicted all this over a decade ago and Baylor confirmed it.

#10

Yeah I also find this mad. And then theres people who got both…