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Androgen Receptors Have Effect On Brain? Any Proof?

Posted on Wed, 30 Oct 2013

Question: Hi . I understand androgens have effect on brain ie masculanization during baby phase of life. What proof is there that this effect occured via androgen receptor? Has ar receptor been identified in lab from brain of dead baby for example?

Thanks and best regards

Answered by Dr. Lohit K (6 hours later)

Brief Answer:
Yes. Studies have shown the effect.

Detailed Answer:
Hi XXXX, Thanks for using XXXXXXX

Yes. androgen receptors are present in brain. This has been tested in animals and also in humans to study the function of androgen/androgen receptor. You can refer the following study. The author has clearly mentioned the role of AR in brain in early life.
XXXXXXX JD (September 2001). "Androgens, androgen receptors, and male gender role behavior". Horm Behav 40 (2): 358–66

Am giving you the short summary of the above study.
Studies of genetic males with impairment of androgen formation or action has consequently prevented the development of the normal male phenotype provide unique insight into the control of gender role behavior and have a female phenotype at birth.
Genetic males with mutations that impair profoundly the function of the androgen receptor are also raised as females and have consistent female behavior as adults.

This suggested the role of androgen and also androgen receptors.

Androgen in prenatal period effect body in two different stages.
1. 1st 3 months: Helps in Genital virilization and development of prostate and seminal vesicles.
2. Second trimester: Gender formation. This period affects the femininization or masculinization of the fetus.

Hope this clarified your doubts. Feel free to ask if you have any further related query.
Wish you good health.
Regards

Above answer was peer-reviewed by : Dr. Chakravarthy Mazumdar

Follow up: Dr. Lohit K (13 minutes later)

Thank you Dr Lohit K for the answer.

Is the above described effects and/or other effects because of conversion to estrogen....or is there evidence of direct Ar Gene expression?

I want something that proves androgen binding to its receptor and then further expressing the gene (in the brain of course)

Maybe the study above is a result of estrogen receptor gene expression?

Hope you can clarify. Thanks and Best Regards

XXXX

Answered by Dr. Lohit K (24 minutes later)

Brief Answer:
Yes due to androgen receptors.Estrogen have a role

Detailed Answer:
Hi, Thanks XXXX for the follow up.

I am writing the details of some study here for your clarification.

This action is mediated by the androgen receptor and not the result of conversion of androgen to estrogen. These are the direct lines selected from the above mentioned article.

Further read the article from hormones and behaviour. This will clear your doubts.
WWW.WWWW.WW
Thesa are direct lines from the study.
Traditionally, masculinization of brain is believed to depend on estrogen receptors (ERs) and not androgen receptors (ARs).
According to the aromatization hypothesis, circulating testosterone from the testes is converted locally in the brain by aromatase to estrogens, which then activate ERs to masculinize the brain. However, an emerging body of evidence indicates that the aromatization hypothesis cannot fully account for sex differences in brain morphology and behavior, and that androgens acting on ARs play a role.

Hope this helps you.

Regards

Above answer was peer-reviewed by : Dr. Chakravarthy Mazumdar

Follow up: Dr. Lohit K (21 hours later)

Thank you Dr Lohit. Is there any other example for androgen receptor activation going on to express the ar gene?

What about differences in lh fsh patterns between males and females....is this preprogrammed by androgens perhaps through ar gene?

I urgently need proof to help me feel at easse. Kind regards

Answered by Dr. Lohit K (19 hours later)

Brief Answer:
Pre programmed by chromosomes (X & Y).

Detailed Answer:
Hi XXXX, thanks for the question.

First I take LH and FSH pattern.
The release of these gonadotropins depends on pattern (amount, frequency and timings) of release of GnRH and inhibin and mainly by feed back mechanism of testosterone in males and estrogen and progesterone in females. These are more active after puberty and all these are physiologically determined (Programmed) based on their genetic makeup (Chromosomes). That's why we see lot of differences in hormone release and its effects.
Testosterone is weaker than estrogen in inhibiting Gn secretion, but has effect on both FSH and LH.

For human examples for activation of AR genes, I searched in many journals but only found animal studies. In textbooks I found that androgen act through the AR receptor in brain.
There are lot of research going on this concept.

So in nutshell both androgen and estrogen receptors act in brain for regulation.

Hope this helps you.

Regards

Above answer was peer-reviewed by : Dr. Chakravarthy Mazumdar

Follow up: Dr. Lohit K (1 hour later)

Thanks for your time and answer.

For final clarification, in healthy subjects without genetic defects does androgen acting through ar receptor mean subsequent action in ar gene?

Best regards

Answered by Dr. Lohit K (9 hours later)

Brief Answer:
No. Subsequent action may be on other genes

Detailed Answer:
Hi, thanks for follow up question.

Androgen after acting on its receptor affects the genes in nucleus. These are generally present in all cells and need not be single gene. They affect the cellular mechanisms (protein synthesis and other functions) and get the response. The same response can be obtained by other related hormones also based on the function required.

AR gene helps in producing the androgen receptor. Androgen after acting on the receptor does not required the gene responsible for producing androgen receptor for the later mechanism.

Hope this clarifies your doubts.

Wish you good health.
Kind Regards

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Above answer was peer-reviewed by : Dr. Chakravarthy Mazumdar