Inflammation-Induced TLR4 Expression And Reactive Oxygen Species Are Attenuated By Dihydrotestostero

[Drareg]

Abstract
Our previous data have shown that dihydrotestosterone (DHT) attenuates endotoxin and oxygen glucose deprivation (OGD)-induced cyclooxygenase-2 (COX-2) in human vascular smooth muscle (VSM) cells. COX-2 plays a role in vascular inflammation and has been implicated as a source of reactive oxygen species (ROS). In rats, androgens have been shown to be protective during cerebral ischemia and to decrease oxidative stress in vascular tissues. Because TLR4 has been implicated in injury-induced oxidation, we hypothesized that chronic DHT treatment (10nM) alleviates oxidative stress by attenuating TLR4 expression and decreasing ROS following endotoxin, hypoxia, or OGD in primary human VSM cells. TLR4 localization was detected via confocal microscopy, TLR4 protein levels were measured via western blot, and ROS generation was measured using the indicator dye carboxy-H2DCFDA. Endotoxin, hypoxia, and OGD all increased TLR4 expression compared to controls. In contrast, endotoxin and OGD-induced TLR4 expression was attenuated in the presence of DHT. In the OGD studies, DHT’s effect on TLR4 was androgen receptor independent. Similar to the TLR4 studies, cytokine-induced ROS production was blunted by DHT. Thus in conditions of oxidative stress, androgens may confer protection from vascular injury in part by attenuating both TLR4 expression and ROS production. Sarver Heart Center and AHA (RG & KO)

Inflammation-Induced TLR4 Expression and Reactive Oxygen Species are Attenuated by Dihydrotestosterone in Human Primary Vascular Smooth Muscle Cells

 

[Dante]

. In the OGD studies, DHT’s effect on TLR4 was androgen receptor independent.

Inflammation-Induced TLR4 Expression and Reactive Oxygen Species are Attenuated by Dihydrotestosterone in Human Primary Vascular Smooth Muscle Cells

This is the full dissertation of the first author Kristen Leanne Osterlund
which lead to this paper.
http://dspace.library.colostate.edu..._items/csu01_storage/2012/03/01/file_1/123369

She says that DHT's protective are due to ER-beta receptors which happens to be activated by 3β-diol .
3β-diol, is an endogenous steroid hormone. It is a 5α-reduced and 17β-hydroxylated metabolite of dehydroepiandrosterone(DHEA) as well as a 3β-hydroxylated metabolite of dihydrotestosterone (DHT).
3β-Diol is a selective, potent, high-affinity full agonist of the ERβ, and hence, an estrogen

So, is there a good estrogen ?

 

[Drareg]

This is the full dissertation of the first author Kristen Leanne Osterlund
which lead to this paper.
http://dspace.library.colostate.edu..._items/csu01_storage/2012/03/01/file_1/123369

She says that DHT's protective are due to ER-beta receptors which happens to be activated by 3β-diol .
3β-diol, is an endogenous steroid hormone. It is a 5α-reduced and 17β-hydroxylated metabolite of dehydroepiandrosterone(DHEA) as well as a 3β-hydroxylated metabolite of dihydrotestosterone (DHT).
3β-Diol is a selective, potent, high-affinity full agonist of the ERβ, and hence, an estrogen

So, is there a good estrogen ?

That's a good question,from what I understand we do need estrogen in small amounts,problem is excess.

Is her interpretation the only possible interpretation of the results?

 

[haidut]

That's a good question,from what I understand we do need estrogen in small amounts,problem is excess.

Is her interpretation the only possible interpretation of the results?

DHT itself, like all other 5-AR derived androgens is an antagonist on the TLR4 receptor. The metabolite 3-beta androstenediol is also a TLR4 antagonist even though it happens to be partially estrogenic. As a comparison estrogens that are all agonist of the ERbeta receptor like estradiol, and estrone are NOT protective against endotoxin and are NOT antagonist of TLR4. I suspect she simply got pushed to find an explanation that did not involve giving too much credit to DHT. After all, we all know that DHT causes prostate cancer and balding, right? Right??

 

[Drareg]

DHT itself, like all other 5-AR derived androgens is an antagonist on the TLR4 receptor. The metabolite 3-beta androstenediol is also a TLR4 antagonist even though it happens to be partially estrogenic. As a comparison estrogens that are all agonist of the ERbeta receptor like estradiol, and estrone are NOT protective against endotoxin and are NOT antagonist of TLR4. I suspect she simply got pushed to find an explanation that did not involve giving too much credit to DHT. After all, we all know that DHT causes prostate cancer and balding, right? Right??

I didn't want to be cynical and all but I was guessing in that direction.
Either way it seems to lower ROS.

 

[Dante]

DHT itself, like all other 5-AR derived androgens is an antagonist on the TLR4 receptor. The metabolite 3-beta androstenediol is also a TLR4 antagonist even though it happens to be partially estrogenic. As a comparison estrogens that are all agonist of the ERbeta receptor like estradiol, and estrone are NOT protective against endotoxin and are NOT antagonist of TLR4. I suspect she simply got pushed to find an explanation that did not involve giving too much credit to DHT. After all, we all know that DHT causes prostate cancer and balding, right? Right??

She says that she used androgen receptor antagonist and estrogen receptor antagonist( names of drug included in dissertation) to pinpoint which one does that.
If anyone here does mice research, he/she can verify her claims.
As for DHT causing prostate cancer, even Wikipedia has caught up to latest studies stating dht role in prostate cancer has been disproven.
MPB - no one seems to be Able to crack the code.

 

[haidut]

She says that she used androgen receptor antagonist and estrogen receptor antagonist( names of drug included in dissertation) to pinpoint which one does that.
If anyone here does mice research, he/she can verify her claims.
As for DHT causing prostate cancer, even Wikipedia has caught up to latest studies stating dht role in prostate cancer has been disproven.
MPB - no one seems to be Able to crack the code.

Woo-hoo! Finally, Wikipedia has shown some sense. Please post the quote from the Wiki article here as Wikipedia is edited all the time and that statement may disappear overnight due to pharma editing brigades working overnight. Better yet, please save a copy of the Wiki page as a PDF file and upload here as evidence that you were not making stuff up.
And don't worry, the DHT role in MPB is becoming clearer, it will just take some time like the prostate cancer fiasco. MBP and prostate cancer are highly correlated. If DHT has no role in prostate cancer then it probably does not have that big of a role in MPB either. It may be one of the factors, but its current status as the main villain is laughable.

 

[Dante]

Woo-hoo! Finally, Wikipedia has shown some sense. Please post the quote from the Wiki article here as Wikipedia is edited all the time and that statement may disappear overnight due to pharma editing brigades working overnight. Better yet, please save a copy of the Wiki page as a PDF file and upload here as evidence that you were not making stuff up.
And don't worry, the DHT role in MPB is becoming clearer, it will just take some time like the prostate cancer fiasco. MBP and prostate cancer are highly correlated. If DHT has no role in prostate cancer then it probably does not have that big of a role in MPB either. It may be one of the factors, but its current status as the main villain is laughable.

It's there in pathology section of DHT Wikipedia page.
There is a theory/hypothesis of dht changing skull shape and that indirectly causing vasoconstriction of capillaries leading to hair loss.
Minoxidil doesn't affect dht but is a potassium channel opener and increases hair growth.
Don't know how a potassium channel opener cause hair growth ( not even researchers claim to understand it since it doesn't line with their DHT obsession).

 

[Drareg]

It's there in pathology section of DHT Wikipedia page.
There is a theory/hypothesis of dht changing skull shape and that indirectly causing vasoconstriction of capillaries leading to hair loss.
Minoxidil doesn't affect dht but is a potassium channel opener and increases hair growth.
Don't know how a potassium channel opener cause hair growth ( not even researchers claim to understand it since it doesn't line with their DHT obsession).

Changing skull shape is interesting, does this imply the masculine jaw shape also?
Any link to that article?

 

[Dante]

Changing skull shape is interesting, does this imply the masculine jaw shape also?
Any link to that article?

No really jaw shape, rather the fat/tissue distribution
This is just a theory/hypothesis put forward by a plastic surgeon
Cause of Androgenic Alopecia: Crux of the Matter
Do read this.

 

[lvysaur]

Changing skull shape is interesting, does this imply the masculine jaw shape also?
Any link to that article?

I don't know if I would call it a "masculine" jaw shape, since "masculine" seems to imply "desirable".

The shape is basically a lengthening of your chin, and depth projection of the back of your head. Basically your head gets longer (up/down direction) and deeper (front/back direction). The jaw retreats, so your head looks thinner in the left/right direction. Your face ends up looking more like an invert triangle than a rectangle.

No really jaw shape, rather the fat/tissue distribution
This is just a theory/hypothesis put forward by a plastic surgeon
Cause of Androgenic Alopecia: Crux of the Matter
Do read this.

I can guarantee that the actual bone in the jaw, and rest of the head, changes shape, at least in some people.

I can personally feel bumps of recalcification come and go in a matter of minutes.

 

[Dante]

Woo-hoo! Finally, Wikipedia has shown some sense. Please post the quote from the Wiki article here as Wikipedia is edited all the time and that statement may disappear overnight due to pharma editing brigades working overnight. Better yet, please save a copy of the Wiki page as a PDF file and upload here as evidence that you were not making stuff up.
And don't worry, the DHT role in MPB is becoming clearer, it will just take some time like the prostate cancer fiasco. MBP and prostate cancer are highly correlated. If DHT has no role in prostate cancer then it probably does not have that big of a role in MPB either. It may be one of the factors, but its current status as the main villain is laughable.

@haidut , see the pathology section of the article. I have uploaded the pdf of the DHT wikipedia page . The DHT and prostate cancer thing still persists in the article

Wikipedia is edited all the time and that statement may disappear overnight due to pharma editing brigades working overnight

No offense bro, but i think you read too many conspiracy theories.

 

[Dante]

I can personally feel bumps of recalcification come and go in a matter of minutes.

What's the feeling of calcification like ?

 

[haidut]

@haidut , see the pathology section of the article. I have uploaded the pdf of the DHT wikipedia page . The DHT and prostate cancer thing still persists in the article

No offense bro, but i think you read too many conspiracy theories.

No offense either, but I speak from experience. Search the forum for my post on estrone sulfate being prognostic for prostate cancer. That statement came from Wikipedia and is no longer there. I have a friend who works for a major PR company and one of their big contracts is to edit Wikipedia according to the wishes of their Big 5 pharma client. There are over 70 people working on just this one contract, for this one drug company, and for this one drug the company sells. Do you understand the significance of this? There are 70 people doing nothing else but editing Wikipedia to twist perception in favor of a paying client.
Did you not see the news about the US Senators hiring PR firms to edit Wikipedia not only to bash their opponents and invent fake scandals but also to edit the Wikipedia pages of major donors to their opponents and adding stuff about non-existent litigations or deleting posts about ongoing litigations?
The Covert World of People Trying to Edit Wikipedia—for Pay
United States Congressional staff edits to Wikipedia - Wikipedia, the free encyclopedia
Can pharma companies edit Wikipedia? - The Medical Futurist
BBC NEWS | Technology | Congress 'made Wikipedia changes'
Who in the Senate Edited Rick Santorum's Wikipedia Page to Say He's From "Fart, Virgin"?
FL Senate Candidate Tries To Edit Scientology Links From Wikipedia Page, Streisanding Those Links Everywhere
http://talkingpointsmemo.com/livewire/senate-staffer-fails-to-remove-torture-reference-Wikipedia
GOP Senate campaign admits to editing its candidate's Wikipedia

 

[lvysaur]

What's the feeling of calcification like ?

Like little hard bumps on the jawline.

 

[youngandold]

Interesting post about big pharma editing wiki.

I doubt skull changes CAUSE Mpb
Rather androgens in men cause skull changes over decades beginning in the growing years.

 

[Dante]

Interesting post about big pharma editing wiki.

I doubt skull changes CAUSE Mpb
Rather androgens in men cause skull changes over decades beginning in the growing years.

not exactly skull/jawline changes but fat/tissue distribution over the top of the head , a plastic vascular surgeon may better know about it.