BRyaN: more q's about ARs

[jimmystanley]

just have been thinking about this process (but i still know jack so it's all pseudo)

1. if taking propecia can cause an upregulation of AR's in certain hair follicle cells wouldn't this also cause an upregulation in those cells that are associated with sex drive? (again...this is just mumbo jumbo thinking...not sure how any of this takes place)

2. you said that some cells can up regulate to about 2 - 5 000 AR's per cell.... that seems like quite a bit...do you think that a good anti androgen (RU or fluridil) can actually tackle that many AR's per cell??

3. if we manage to inhibit those androgen receptors properly how do we know that this also won't cause any male pattern baldness related inflammation in the same way that DHT and T does?

thanks a lot...sorry if these questions are non-sense

 

[chewbaca]

BTW has it been proven that propecia upregulates AR?

THen what happened to genetics? SO genetics are being modified? it doesnt make sense.....U cant modify genetics just by popping a pill?...


so if someone invents a pll which can downregulate ARs....is it considered a cure?

anyway i just got a Q....what does one mean exactly by the term upregulation of ARs?

Let's say a person is destined to be a Norwood 3 till he dies (genetics)..so if he takes propecia, will he be actually changing his Norwood 3 to a worse scenario?.....anyone care to explain?

 

[chewbaca]

Here is something i found but not sure if its relevant tho the thread,,We need bryan to explain pls

J Steroid Biochemistry and Molecular Biology (1990) 37 553. In cultured adipocytes, methyltrienolone and testosterone demonstrated marked upregulation of AR content upon administration of androgen. 10 nanomolar methyltrienolone increased AR content (as measured by binding to radiolabeled androgen) by more than five times, relative to zero androgen.

J Steroid Biochemistry and Molecular Biology (1993) 45 333. In cultured smooth muscle cells from the penis of the rat, mRNA production was found to be upregulated by high dose testosterone (100 nanomolar) or DHT. When 5-alpha reducatase was inhibited by finasteride, thus blocking metabolism to DHT, AR mRNA production was downregulated in response to testosterone. Blockage of the aromatization pathway to estrogen by fadrozole eliminated this downregulation effect. Estradiol itself was found to downregulate AR mRNA production in these cells.

Endocrinol Japan (1992) 39 235. One nanomolar DHT was demonstrated to increase AR protein by over 100% within 24 hours, relative to zero androgen level. The half life of the AR was demonstrated to increase from 3.3 h to 7.5 h as a result of the androgen administration.

Endocrinology (1996) 137 1385. 100 nanomolar testosterone was found to increase AR levels in vitro in muscle satellite cells, myotubes, and muscle-derived fibroblasts.

http://www.steroidology.com/forum/archive/index.php/t-390.html

 

[jimmystanley]

i hope that is the case...but i remember reading some stuff that bryan posted about inhibiting alpha 5-r causing androgen sensitive cells to create more androgen receptors.. i'm not sure how to post other people's posts.

 

[Cassin]

. i'm not sure how to post other people's posts.

You mean quote? Look at the top right of the message and hit quote. Nice and easy.

 

[Bryan]

just have been thinking about this process (but i still know jack so it's all pseudo)

1. if taking propecia can cause an upregulation of AR's in certain hair follicle cells wouldn't this also cause an upregulation in those cells that are associated with sex drive? (again...this is just mumbo jumbo thinking...not sure how any of this takes place)

It's possible, but just because it happens in one specific type of cell doesn't necessarily mean that it happens in another. You'd have to test each cell type individually, to know for sure.

2. you said that some cells can up regulate to about 2 - 5 000 AR's per cell.... that seems like quite a bit...

That's not exactly what I said. This is from "2nd Edition Physiology", Bullock et al, copyright 1991, Williams & Wilkins (page 341):

"Steroid enter target cells and bind to specific mobile receptors in the cytoplasm. The hormone-receptor complex then binds to specific DNA sequences to initiate transcription and translation. Approximately 3,000 to 10,000 intracellular receptors exist per steroid target cell"

do you think that a good anti androgen (RU or fluridil) can actually tackle that many AR's per cell??

Sure. Antiandrogens have proven effects.

3. if we manage to inhibit those androgen receptors properly how do we know that this also won't cause any male pattern baldness related inflammation in the same way that DHT and T does?

I'm not entirely sure I understand your question. If androgens cause inflammation (either directly or indirectly) via binding with the androgen receptor, then BLOCKING the androgen receptor ought to stop that process.

Or did you have something else in mind that I didn't catch?

Bryan

 

[Bryan]

BTW has it been proven that propecia upregulates AR?

Sawaya claims to have found that in the hair follicle cells of finasteride users, but another famous hairloss doctor seems to doubt that finding.

THen what happened to genetics? SO genetics are being modified? it doesnt make sense.....U cant modify genetics just by popping a pill?...

In a certain sense, I guess you could say that. You can modify the cellular production of a great many substances, just by popping various drugs and chemicals! Of course, it's usually a TEMPORARY alteration...

so if someone invents a pll which can downregulate ARs....is it considered a cure?

Would YOU consider it a "cure" if you had to take it every day?

anyway i just got a Q....what does one mean exactly by the term upregulation of ARs?

An increase in the "normal" cellular production of androgen receptors.

Let's say a person is destined to be a Norwood 3 till he dies (genetics)..so if he takes propecia, will he be actually changing his Norwood 3 to a worse scenario?.....anyone care to explain?

I don't understand the question. Why do you think Propecia would make his condition WORSE?? Propecia has been proven in numerous studies to fight male pattern baldness.

Bryan

 

[chewbaca]

BTW has it been proven that propecia upregulates AR?

Sawaya claims to have found that in the hair follicle cells of finasteride users, but another famous hairloss doctor seems to doubt that finding.

THen what happened to genetics? SO genetics are being modified? it doesnt make sense.....U cant modify genetics just by popping a pill?...

In a certain sense, I guess you could say that. You can modify the cellular production of a great many substances, just by popping various drugs and chemicals! Of course, it's usually a TEMPORARY alteration...

so if someone invents a pll which can downregulate ARs....is it considered a cure?

Would YOU consider it a "cure" if you had to take it every day?

anyway i just got a Q....what does one mean exactly by the term upregulation of ARs?

An increase in the "normal" cellular production of androgen receptors.

Let's say a person is destined to be a Norwood 3 till he dies (genetics)..so if he takes propecia, will he be actually changing his Norwood 3 to a worse scenario?.....anyone care to explain?

I don't understand the question. Why do you think Propecia would make his condition WORSE?? Propecia has been proven in numerous studies to fight male pattern baldness.

Bryan

1) Bryan could u provide us with more info about the doubt about sawaya's findings?

2)Does upregulation of AR refer to sensitivity? or is just a higner number of receptor nodes?

3)So if propecia does upregulate Ars, will a person who was on finasteride for a long time the moment he stops taking it, his male pattern baldness returns more aggrssively due to the upregulation?

 

[Bryan]

1) Bryan could u provide us with more info about the doubt about sawaya's findings?

That was from a well-known researcher into hairloss. If I were to tell you his name, I'm sure you'd recognize it! However, his comments were reported to me by a third party who was in email contact with him, and told me what he said. I don't feel comfortable with telling you his name, because it would be revealing what he told someone privately.

Basically what the fellow said is that finasteride usage is not generally known to be associated with "hyper-androgenic" types of responses, and he even went so far as to subtly question Sawaya's legitimacy as a researcher (remember how there was supposedly some doubt in certain quarters about the validity of her medical degree?).

However, I personally have my own doubts about what that hairloss Doctor himself said; it seems to me that the fact that finasteride isn't generally known for "hyper-androgenic" responses by no means eliminates the possibility that androgen receptors may in fact be upregulated with finasteride usage. I tend to accept what Sawaya said as being quite reasonable.

2)Does upregulation of AR refer to sensitivity? or is just a higner number of receptor nodes?

That's a VERY good question.

By definition, it means an increase in their number. However, there's a great deal of chemistry surrounding the workings of androgen receptors and their ligands. There are many chemical factors which can either INCREASE or DECREASE their effect and their ability to bind with hormones, so it certainly doesn't seem out of the question to me that in addition to increasing the numbers of androgen receptors in certain situations (finasteride usage?), a cell may also alter those other chemical factors in such a way as to make those receptors more potent.

3)So if propecia does upregulate Ars, will a person who was on finasteride for a long time the moment he stops taking it, his male pattern baldness returns more aggrssively due to the upregulation?

I personally think that's a distinct possibility. Take a look at the haircount graph in the original large Propecia trial: in the group that got finasteride for the first year but were then switched over to placebo for the second year, their haircounts dropped at a faster RATE during that second year than the group that got the placebo for the entire duration of the study, although they didn't quite drop to the same actual numerical level as the ones who got the placebo for both years. I always suggest that if you decide to quit using finasteride, maybe you should taper-off the drug slowly, and not quit "cold-turkey".

Bryan

 

[Old Baldy]

Oh Bryan, I'll bet it CAN make the AR's more "potent"? Just a feeling I have, can't prove it, but from all I've read, the human body "adjusts". I have always thought (well since only Sept., 2004 :lol: ) that that might be one of the reasons finasteride. doesn't do so well for alot of guys?

I mean, if the genes say "AR's get that testosterone", then they "get that testosterone"!! :lol: :lol: :lol:

 

[Bryan]

They can obviously "adjust" to a certain limited degree, but they can't completely counteract the effects of powerful antiandrogens and 5a-reductase inhibitors. If they _could_ do that, then finasteride wouldn't have been proven to be effective against hairloss in numerous studies, RU58841 wouldn't have been found to be the most effective agent ever tested (at least in the short-term) for hairloss in stumptailed macaques, James Hamilton wouldn't have found that castration brings balding to a halt, etc. etc.

I may have been the first one to post about Sawaya's finding (the alleged upregulation of androgen receptors) on the hairloss sites a few years ago. As God is my witness, it never even occurred to me at the time that people would be talking about it, ever since! :freaked:

Bryan

 

[chewbaca]

Thanks for the clarification BRYAN.....BTW i feel that 100% DHT inhibition would not result in AR upregulation?

AND also if u can stop and take propecia and alternate between, i mught be able to trick the body into not upregulating ect?

 

[jimmystanley]

3. if we manage to inhibit those androgen receptors properly how do we know that this also won't cause any male pattern baldness related inflammation in the same way that DHT and T does?

I'm not entirely sure I understand your question. If androgens cause inflammation (either directly or indirectly) via binding with the androgen receptor, then BLOCKING the androgen receptor ought to stop that process.

Or did you have something else in mind that I didn't catch?

Bryan[/quote]

what i mean is: if the anti-androgen (what ever it may be) binds to the receptor, what happens to the AR? does it follow the same steps as if it were binded to DHT or T that eventually leads to the miniturization process? if not...does any one know what happens to it.

hope this is more clear

 

[Old Baldy]

Well I hope you guys are right because I'm on 4 months of using finasteride. I'd hate for it to be neutralized by U. R. I really do worry about it.

That's the problem when there isn't a cureall, all these "ideas" and theories crop up as I'm reading them and I say "well.........?".

(Like Jimmy says what happens to the AR's? Do they just go into limbo? Are they constantly being "neutralized" and are always ready to receive androgens if the drug wears off? And on, and on, and on....... into oblivion? For some reason that just doesn't sit well with me.)

 

[jimmystanley]

well, i think eventually the AR's die (or they have a certain life span, not sure how long) but i'm just wondering if after they are binded to the anti androgen if they can still do damage?

 

[Bryan]

Androgen receptors are eventually degraded and replaced with newly synthesized ones.

When an antiandrogen binds to an androgen receptor, the complex is no longer able to bind with DNA in the cell's nucleus to stimulate androgen-sensitive genes. If it WERE still able to do that, why would antiandrogens even be called "antiandrogens" at all?? :wink:

Ok, ok: I'm glossing over a couple of important details here, but the gist of what I just said is correct.

Bryan

 

[Old Baldy]

I see, I had the cart before the horse. Thanks for the explanation.

 

[chewbaca]

i am still starting to have doubts abt sawaya's findings...cause u see, how do we eactly know his findings were concluded by AR upregulation?
let me explain...a person took finasteride for 10 years ect and All finasteride does is inhibit DHT and leaves the receptors alone..

Maybe what sawaya found is the scenario of a person 10 years later if he never took finasteride which mean he will be a total bald..In other words its like a whole male pattern baldness engine working but withut the secret ingredient to produce the final effect - DHT...

Its like a factory whoich works and works but never produces products cause it has an ingredient missing

which this whole thing may go to show that more receptors will only show up with time and be probably be mistaken for some external agent like finasteride causing the effect...

and also i still doubting. if male pattern baldness is controlled by genetics , why does upregulation still work?.it means that n fact u are alterng what's already predetermined?......that means u are altering the genetic makeup itself..

well i am beginning tot hink that what sawaya found is the Androgen receptors which show ups over time......

 

[Bryan]

i am still starting to have doubts abt sawaya's findings...cause u see, how do we eactly know his findings were concluded by AR upregulation?

FYI: Dr. Mary ("Marty") Sawaya is a woman.

let me explain...a person took finasteride for 10 years ect and All finasteride does is inhibit DHT and leaves the receptors alone..

Maybe what sawaya found is the scenario of a person 10 years later if he never took finasteride which mean he will be a total bald..In other words its like a whole male pattern baldness engine working but withut the secret ingredient to produce the final effect - DHT...

Its like a factory whoich works and works but never produces products cause it has an ingredient missing

which this whole thing may go to show that more receptors will only show up with time and be probably be mistaken for some external agent like finasteride causing the effect...

The alleged "intense upregulation" showed up after using finasteride for only 6 months, and I suspect it actually happened a lot sooner than that. It was CLEARLY a result of the finasteride.

and also i still doubting. if male pattern baldness is controlled by genetics , why does upregulation still work?

It's just a natural balancing mechanism in the cell. It's the cell's way of attempting to get back its normal level of androgenic stimulation.

.it means that n fact u are alterng what's already predetermined?......that means u are altering the genetic makeup itself..

It's not exactly "predetermined" in the way that you're hinting at. There's apparently homeostasis in the cell that wants to maintain a certain level of androgenic stimulation. If you interfere with it by stopping the production of DHT, the cell just naturally tries to restore that androgenic stimulation with a feedback mechanism which increases the production of androgen receptors.

well i am beginning tot hink that what sawaya found is the Androgen receptors which show ups over time......

Nope. Definitely not.

Bryan

 

[chewbaca]

So Bryan, it means that the genetic theory doesnt work anymore if u try to inhibit male pattern baldness?

so this means the watever gene theraphy out there isnt going to work cause in the end AR upregulation occurs?

if that's the case why does hair transplant still work?....The cells could again modify themselves and reject the new hair right?