Does DNP increases Androgen Receptor Density ?

This is a copy paste of a post and thread made on Facebook, added here so that it is not lost to time on Facebook. 

Someone from the PED Education Community asked me to comment on this

Bro Science or True ?

” DNP increases Androgen Receptor Density ”

Yes I agree there are some interesting technical points here

There are studies that look at the Dynamic status of Prostate Androgen Receptors, and several that show the effect of DNP on the Androgen Receptor in that Organ.

My takeaway from those studies is this

That in the Rat Prostate, the androgen receptor can go through inactivation-reactivation processes as well as ” recycling” and here the term ‘activation’ represents the intracellular process by which receptor that does not bind steroids is converted into a steroid-binding form.. and this process is influenced by DNP.

Thats certainly interesting

But for me this is hardly unequivocal proof that for our Tribe in Human Skeletal Muscle Tissue DNP upregulates the Androgen Receptor

For me to accept that as “fact” rather than interesting idea ..

I would need to see a study in Humans that actually looks directly at that in Human Skeletal Muscle as we see here in the second image where ” Muscle Androgen Receptor Content but Not Systemic Hormones Is Associated With Resistance Training-Induced Skeletal Muscle Hypertrophy in Healthy, Young Men ” – for me that is evidence that we can quote.

The idea that DNP can influence the AR inactivation-reactivation processes in Rat Prostate, at this time does not cross that line into “things we know” for me at least

Rather it might be true sure

But there are lots of follow on questions, the simplest of which is at what dosage and time duration ? etc

For DNP is not something you should simply live on..

Ideas ?

Lets hear them, by all means this one has been around 30 years + …. but be very careful in confusing someones ideas and ” evidence” – they are not necessarily the same thing

Scott HowellScott Stevenson.. anyone else if you have have anything to add to this.. even some evidence than I have not seen to support or refute this ? Most appreciated

Just by way of bolt on information here

DNP is one of those Drugs that you need to very careful with guys

There are actually quite a lot of studies that look at the many potential adverse events that can be associated with its use.

And like all Drugs the Dosage is the Poison, you can see my usage level at 100mg a Day vs these studies.

Victor Black

Thomas Calhoun My main question with any new findings in this circle is the same everytime. Do these numbers have real world application and if so, would it be worth the risk of such a dangerous compound?

Victor Black 

Certainly not new findings most the studies on DNP date back to the 1930’s time frame when it was in Human Use.

and these studies from the 1980 – 1990 time frame – rodent models

I totally agree that this must be considered a dangerous compound for those that abuse it or misuse it.

100% agree

But Trenbolone is a Chemical Uncoupler, Thyroid T3 is a Chemical Uncoupler and there a lot of research into next generation Chemical Uncouplers for the Treatment of Obesity.

So we have to ask ” why” is this compound so dangerous ?

Because peple dont know what it is
Because people dont understand how it works
Because people use truly abusive dosages of it

ie well 1 works great so I will take 5 !

That is my argument against Insulin

If people dont know what it is
If people dont understand how it works
If people use truly abusive dosages of it

You can kill yourself !

How exactly are you going to kill yourself using 6IU of Humalog a Day ?

How exactly are you going to kills yourself using 50 – 100mg of DNP for 2 weeks ?

By using 10 times that is the answer

100mg a Day results in an increase of around 11 % BMR in Humans, why would you need more than that ?

Most people dont even start talking about DNP at the dosages I personally use..

ie 1mg/kg/day

Thomas Calhoun I’ve never used it, I have contemplated it, but I don’t know enough about it to mess with it.

Victor Black

Kudos to you then

IMO 99% of people that use these compounds and get into trouble with them precisely because they dont have that ” survival mechanism”

ie I dont know what I am doing, so I will not mess around with it.

Rather, their educational model consists of

” my mate said its great so I will use it.. ”

How much Bro.. ” ah” .. 600mg a Day ? Lets use that

Idiot.

Thomas Calhoun Considering I can just hone in on my diet and achieve the same results as DNP, it just takes longer, why risk it? I work construction, which requires my body to have a certain level of health to maintain everyday life. I can’t sit around with the AC on with a bucket of ice…

Victor Black Thomas Calhoun 100%.. where its a consideration is here

In the clinically obese under Medical Supervision I support the use of Chemical Upcouplers, sure.

In Enhanced Rapid Fat Loss Model for Advanced, I say again Advanced Users.. why not ?

Again if you even notice your Temp rising to the degree to need to sit in front of a fan your abusing the Drug

Its no different in regard to Insulin or Trenbolone

If you go Hypo on Insulin you are using too much

If you cant sleep and wake up in a puddle of sweat your using too much Trenbolone

Same thing really if just another Drug for us to use or Abuse where abuse can lead to your demise.

There is the good the bad and the ugly for DNP just like every other drug

But the bucket of ICE idea you talk about ?

Thats is not even close to “use” of a Chemical Uncoupler .. that is the outcome from stupidity plain and simple

Scott Stevenson There are a few underlying assumptions that would make the finding relevant to skeletal muscle growth (in humans):

As you noted, Victor, there could be species differences.

Androgen receptor function / signaling in these different tissues / organs and the presence of enzymes skeletal muscle that degrade DHT (not found in prostate).

To what extent – THIS IS THE BIG ONE – the receptor content reflects signal transduction (transactivation), i.e., does more androgen receptor equate automatically to a greater anabolic / androgenic signal? Given the complexity of co-regulation and androgen action, not to mention the oft-forgotten megalin receptor, I’m thinking that’s overly simplistic.

1. Heinlein CA, and Chang C. Androgen Receptor (AR) Coregulators: An Overview. Endocr Rev 23: 175-200, 2002. https://doi.org/10.1210/edrv.23.2.0460

1. Adams JS. Bound to Work: The Free Hormone Hypothesis Revisited. Cell 122: 647-649, 2005. http://dx.doi.org/10.1016/j.cell.2005.08.024

Scott Howell Nice mention of megalin. Not many people mention it but its discovery was a seminal step in research of this area. It is overly simplistic even in the scope of SHBG levels as well in regards to mediation of local sex hormone effects. My mind goes to ARE-independent signaling where transcription occurs but not directly just like with ER and of course membrane-associated G protein signaling. We know AR will upregulate in most all tissue except the prostate and there is no ceiling I can find for this. We also know that the control of AR is autoregulation (the same process for many steroid hormones) that is dose responsive. So reasonably if we consider the extent to which AR upregulation or increase expression equate to actual transcription and translation of proteins, then it seems likely that classical genomic signaling proceeds as it would but any other signaling that is response element independent or non-genomic (non-classical) might proceed differently. Were you thinking of all these acting independently or separately?

Scott Stevenson Scott Howell I was mainly just considering the overly simplistic notion (IMO) that AR receptor concentration generally speaking, without considering location (PM vs. cytosolic) and the SHBG / Megalin receptor (not to mention differential binding of differing AAS to the AR and tissue, species and even sex-specific metabolism / pharmacodynamics/kinetics of AAS), doesn’t really have a much value when it comes to inferring what might be happening in (human) skeletal muscle.

This is your area I believe, so I certainly defer to your expertise, of course!!!

Considering though that DNP creates an energy drain (ATP demand via uncoupling ox. phos.) I would not expect it to produce favorable effects on muscle protein metabolism, at least for those looking for larger muscle cells. 🙂

And this is where I think many folks are going with an effect on AR, i.e., that if AR levels go up (without any further nuance) or some kind of up regulation is noted that this is synonymous with positive protein balance and sk. muscle hypertrophy. That seems to be quite a leap.

(In other words, I wasn’t suggesting anything as far as the coupling of membrane vs. cytosolic [AR]. :))

Scott Howell Scott Stevenson Understood. I was hoping there was something I was unaware of. We go through the literature over and over and each time personally I see a nuance or something that adds to my understanding. I am fully on board with your thoughts on DNP. I have several case reports on DNP. Some case series of occupational workers and others just bodybuilders. All of them show severe tissue damage and it is one of the compounds I try to steer people away from, not only for the acute and severe hyperthermia but also the long-term residual effects are just not known. The effective dose is just to close to a lethal dose than I am comfortable with when in bodybuilding as you assuredly know, the more is always better paradigm is rampant. One case in particular of a teenage girl pops in my mind and the organ sections and tissue damage was something I had never seen before in terms of magnitude and severity. We are definitely on the same page. We should tackle a peer review submission some time in the near future. Are you still in academia or affiliated with a university lab?

Scott Stevenson Scott Howell That’s really unfortunate to hear about the teenage girl. I interact with so many individuals who let on inadvertently that they are lacking in what I would consider to be enough knowledge to understand the risks they might be taking (not to mention manage adverse effects…).

My last official U. affiliation was with U. Tampa as an adjunct, and I make it down there occasionally (I did a guest lecture actually on the topic of AAS where I was there last to teach), but no official affiliation currently. (And I would suspect that can most certainly be a hurdle for publication in many instances. EDIT: I would be interested in collaborating, however!)

I just ran a quick search and this paper was just published earlier this year (I was not aware):

https://link.springer.com/article/10.1007/s00204-020-02675-9

Scott Howell Scott Stevenson It is no barrier really about affiliation for publication unless its one of the top tier journals, most of which publish garbage. The only time I ever had a journal verify my affiliation was when the low-CHO zealots accused me of ties to the supplement industry on a submission to the American Journal of Physiology Endocrinology and Metabolism. You are good to go. Not an issue. Regardless, the reason I asked was I thought you might have access to a lab to do some benchwork. I have a couple thoughts on some publications in this area. I keep several projects going at any one time so shoot me a message when you get the time and less hash out a very meaningful topic to shed light on. You know as well as I do that a lot of literature in this area is less than stellar. Btw-the Springer review is pretty solid with good information. I remember pulling it and using some figures in a PPT.

Victor Black Thank you for your input, most grateful.

Re the LD50 for this compound, perhaps this is something we can discuss further at another time for I am aware at this time at least of the concerns over the proximity between effective dosage and lethal dosage.

This is often quoted in older literature however it does seem to be contradicted at least to some degree by the work in modifiying DNP to a controlled-release oral formulation of DNP, CRMP (controlled-release mitochondrial protonophore), that produces mild hepatic mitochondrial uncoupling.

In this work they consider the “effective dosage” of DNP to be very small ie around 0.5mg/kg

Further that elevated body temperature is consequential to what I see as very high dosages, fiqure A and B below

and the LD50 of DNP to be approx 40 to 50 times the dosage I use..

Obviously the difference of 4 x the often quoted between effective dosage and Lethal Dosage is far too close for comfort for me ouch

If its was 4 x times as I have read several places I would bot be interested

But 40 X ? or maybe even 80 x

I have used DNP at 50mg a Day and its ” effective” observationaly

My own question here is what is an acceptable margin of safety ?

and if we dont see an elevation of body temp does this remove the concerns ?

I totally agree with the idea that guys sitting on a couch with a fan blowing over an ice bucket its ludicrous !

As I said above, if you see significantly elevated bodytemp to me that is a huge red flag

Secondly does data collected in a “positive light” as in this study looking at how we can leverage this compound bias the risk ?

IE do the authors of studies downplay the risk to serve their own biases ?

Do the authors mark up the real risk for the same reason

LD50 should be LD50.. at least in my opinion

How is it shown here to be 40 + mg/kg if its not ?

Totally agree that this is not a compound for beginners and easy to say ” dont use it” as always I am trying to learn so that I can try to convince those that do use it might use the minimal effective dosage rather than the stupid dosages I see quoted online

In my experience its easier to say ” use less” than ” dont use it at all”

https://science.sciencemag.org/content/347/6227/1253?

Perhaps on a Podcast we can discuss this

Thank you again

For anyone following this thread

This is the best way I can describe what the researchers did to modify DNP to make its safety profile ” acceptable” for reconsideration for Human Trials

To be clear the drug is NOT approved for Human Use NOT

Effectively Controlled-release mitochondrial protonophore ( CRMP ) is a time released modification of DNP designed to deliver 1mg.kg over a 24 hour period

Lowering the peak Plasma Concentration of DNP in the blood

See fiqures A and B

A is DNP
B is the time release formulation

With dosage response shown in C and D respectively

Scott Howell In every tissue I have pulled studies on, AR will upregulate in a dose response with no identifiable upper ceiling. My first physiology professor in the early 2000s mentioned something similar but I did not internalize it until 10 years later. The prostate AR expression is different from normal tissues. For example, there seems to be a threshold of expression otherwise the saturation model by Morgentaler et al. would not work. Second, in castration resistant prostate cancer the autoregulation of AR at the tissue level of control is flipped (paradoxical) i.e. AR upregulates with decreasing androgen levels. This is the rationale for bipolar androgen therapy with supraphysiologic androgen doses to treat castration resistant prostate cancer. The simplest answer here is the prostate tissue does not regulate AR like any other tissue, so the effects of DNP if they are real do not apply to other tissues of the body. Is the term “density” being used to describe increased AR expression or something else? Can you post the link to the study?

Victor Black

https://portlandpress.com/…/Intracellular-inactivation…

https://www.springer.com/gp/book/9789401172585#

Page 162

Some follow on notes after reading the studies above

1, ” A study in rats that proved 2,4-DNP LD50 to be 30–40 mg/ kg body weight, showing the labelling of Acute Tox. 2 to be more adequate. ”

Correction to my statement that I believed the LD50 to be between 40 – 50mg/kg

I think its prudent to accept the lower value.

Restating my personal use, is at 1 mg/kg – 30 – 40 times below that level

However

In observation

Death reports usually refer to lethal doses of 20–50 mg/kg body weight, fatalities have also been described for 2,4-DNP doses below this level.

Apart from increased basal metabolism and weight loss, the most frequently described symptoms after acute exposure to 2,4-DNP are hyperthermia, nausea, vomiting, confusion, dizziness, headache, agitation, breathing difficulties, back and abdominal pain, tachycardia, diaphoresis, and tachypnoea

Hyperthermia is particularly detrimental to human health and is the limiting factor for 2,4-DNP dose escalation. Exacerbated increases of body temperature up to 44 °C have been linked to fatal 2,4-DNP overdoses (Grundlingh et al. 2011). Moreover, chronic oral exposure to the drug leads to skin and ocular lesions and causes detrimental effects on the bone marrow, central nervous system, and cardiovascular system. Acute renal failure is another serious consequence of 2,4DNP toxicity, evidenced by the existence of tubular necrosis, shown in autopsy of fatal cases

The table before shows fatalities that occurred between 1916 and 2019, relating to exposure to 2,4-dinitrophenol (2,4-DNP)

This is potentially a dangerous compound that can kill !

My goal here is NOT to encourage the use of DNP

Rather to ask why do you need to use so much ?

if 50mg or 100mg works great.. then why are there guys using 500 – 1000mg a day ?

Please share this post

Wishlist Member WooCommerce Plus - Sell Your Membership Products With WooCommerce The Right Way .