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Receptor Upregulator


What do you guys think of this product?


I have found this post on another site from the guy who made it..

Many people asked for the full article, but I didn't want to steal the MD thunder. It is now on the news stands and here is the reprint of the article.

Oh, we also are a little delayed because AND THIS IS BIG:


It will work with ANY test booster, anti-estrogen, prohormone or steroid! We will be offering this ingredient to KEY supplement companies and including it in our own products as a gesture of good will in the industry!

SIRT1 Inhibitor Up-Regulates Androgen Receptor Levels

To say that androgens down regulate androgen receptor levels is darn near heresy in bodybuilding circles. It is cemented in bro-lore that androgens up regulate androgen receptor levels. Unfortunately, as with much of bro-lore, this is simply not true. Let���?�s just look at the ���?anecdotal���? evidence that there is no up-regulation of the androgen receptor on or after a cycle of steroids or prohormones.

If this phenomenon actually existed, your first cycle would be your worst in the form of gains, you would feel the least side effects of androgen use and you would need a high dose to get results. This is clearly not the case, since the first cycle is usually the best in terms of gains, while on the first cycle one usually takes far less total milligrams and side effects like aggression and sleeplessness are usually the most pronounced.

If the androgen receptor up-regulates with steroid use, your first cycle would feel the weakest. Second, you would need to use less steroid or pro-hormone on the second cycle, since the androgen receptor (AR) would be up-regulated, so you could lower your total milligrams per cycle.

I don���?�t know about the guys you hang with, but I have never heard of someone���?�s cycles getting better and better the less they take! Doesn���?�t it make sense that like many tissues in the body, receptors will down regulate in response to excessively high levels of an agonist?

People don���?�t routinely start out taking 500 mg of testosterone enthanate a week and 50 mg of dianabol per day on their first cycle, then the next cycle take the same amount and have better results! Steroid users certainly don���?�t lower their dose of steroids on the second cycle and feel better results.

Sure, someone will quote a study using prostate cancer cells and AR up-regulation or some other nonsense, but prostate cells are not muscle cells and cancer cells are not normal cells anyway. It is actually well documented (1,2,3) in the scientific literature that androgenic stimulation in skeletal muscles results in down-regulation of androgen receptor levels over time, which will result in decreased androgenic stimulation of DNA transcription and translation of new skeletal muscle proteins.

Anyone who has used steroids or prohormones has inevitably noticed that not only over the long haul but also within a single cycle that androgens seem to lose their effectiveness over time.

The first step that many take to overcome down-regulation is to increase their dosage. While this will work in the short term, eventually receptor levels are down regulated further and ultimately a point of saturation is reached where further increases in dosage do not have an increased positive effect but rather only increased side effects.

I remember the first time I ever took a 10 mg tab of LegalGear Methyl 1-Test. I remember being overwhelmed with how ���?strong���? this androgen felt, however by the time it was banned a year later, I could routinely do 40-50mg cycles without any real side effects. I know first hand how the AR down-regulates in response to specific androgens (many of my esteemed colleagues will disagree, but I do believe that switching to a different androgen each cycle makes a difference, but that is a much different discussion).

Many people believe that time off is necessary to ���?clean���? receptors before starting a new cycle. While the concept of ���?cleaning���? receptors is flawed, it does seem that a break from androgens helps to restore some of their effectiveness but most know that even after some time off, the response to androgens never seems to be fully regained. We have noticed with other projects that receptor down-regulation can seemingly last ten years or longer and without some external stimulation, the receptors may never recover to their natural levels.

SIRT1 Inhibitors

SIRT1 is an enzyme known as a NAD+-dependant protein deacetylase. SIRT1 binds to the androgen receptor causing deacetylation and reduction in androgen receptor signaling (3). SIRT1 also interferes with co-activator binding to the androgen receptor ���?? a necessary step in activation of the androgen receptor and DNA binding.

AR resides in an inactive state inside the cell bound by several proteins known as ���?corepressors���?, one of which is SIRT1, that prevent the AR from becoming activated and entering the cell nucleus (FIG. 1).

Androgens bind to androgen receptors resulting in receptor activation and release of the co-repressors. The activated ���?androgen receptor-hormone complex���? (ARC) bind to one another and are then able to enter the nucleus where they recruit ���?co-activators���?, bind to DNA and initiate the production of new proteins (FIG. 2).

SIRT1 inhibitors have been shown in the scientific literature to not only increase androgen induced receptor signaling but also to increase endogenous androgen receptor expression (4).

Another interesting action of SIRT1 is its activation of the forkhead transcription factor FOXO-1, which is implicated in the down-regulation of the insulin-like growth factor-1 (IGF-1) receptor due to decreases in androgen receptor level (5). IGF-1 is one of the proteins that is regulated by the androgen receptor and is a known stimulator of skeletal muscle growth. The down regulation of the IGF-1 receptor reduces the responsiveness of muscle cells to this powerful growth stimulant.

The use of a SIRT1 inhibitor before, during or after a cycle can increase the effectiveness of a cycle, help to prolong the duration of effect of androgens and/or restore androgen receptor levels while preventing the down regulation of IGF-1 receptor levels. As an added benefit, a SIRT1 inhibitor can increase levels of uncoupling protein-2 (UCP2) with a concomitant increase in metabolic rate.

A new product called Receptor from LG Sciences is a SIRT1 inhibitor and up-regulates androgen receptor levels and prevents the down regulation of the IGF-1 receptor resulting in increased responsiveness to endogenous or exogenous androgens while increasing metabolic rate through increased levels of UCP2. Using this product will not only improve the impact of your next cycle but can also help recover your receptor levels post-cycle.
Here is a list of the ingredients in RECEPTOR from LG Sciences.

Dihydrocoumarin - a compound found in Melilotus officinalis (sweet clover) disrupts heterochromatic silencing and inhibits yeast Sir2p as well as human SIRT1 deacetylase activity

nicotinamide - free nicotinamide binds in a conserved pocket on the SIRT1 enzyme that participates in NAD(+) binding and catalysis resulting in inhibition of the enzyme.

These two ingredients inhibit SIRT1 through different mechanisms. Dihydrocoumarin competes with the active site of the enzyme while nicotinamide competes with the NAD+ binding pocket. This two-pronged approach allows for complete inhibiton of the SIRT1 pathway. This combination of ingredients along with the single SIRT1 inhibition properties are patent pending from Intellectual Wellness, licensed to LG Sciences.

They exist in a base of N-Acetyl-Cystine and Zinc Aspertate which are both shown to be beneficial to bodybuilders. NAC is a natural liver detoxifier and Zinc has been shown to normalize androgen receptor functionality.

Bottom Line

That is pretty heavy on the science, however what this product can do is to actually up-regulate your androgen receptors and ���?clean them out���? to put it in ���?bro-speak���?. The cleaning is actually up-regulating of the receptor in an effort to increase the anabolic effect of steroids or pro-hormones from excessive use. The best time to take Receptor is following a cycle of steroids or right before your next cycle or both.


  1. Burnstein KL, Maiorino CA, Dai JL, Cameron DJ. Androgen and glucocorticoid regulation of androgen receptor cDNA expression. Mol Cell Endocrinol. Dec 29;115(2):177-86, 1995

  2. Quarmby VE, Yarbrough WG, Lubahn DB, French FS, Wilson EM. Autologous down-regulation of androgen receptor messenger ribonucleic acid. Mol Endocrinol. Jan;4(1):22-8, 1990

  3. Rance NE, Max SR. Modulation of the cytosolic androgen receptor in striated muscle by sex steroids. Endocrinology. Sep;115(3):862-6, 1984

  4. Fu M, Liu M, Sauve AA, Jiao X, Zhang X, Wu X, Powell MJ, Yang T, Gu W, Avantaggiati ML, Pattabiraman N, Pestell TG, Wang F, Quong AA, Wang C, Pestell RG. Hormonal control of androgen receptor function through SIRT1. Mol Cell Biol. Nov;26(21):8122-35, 2006

  5. Li J, Wang E, Rinaldo F, Datta K. Upregulation of VEGF-C by androgen depletion: the involvement of IGF-IR-FOXO pathway. Oncogene. Aug 18;24(35):5510-20, 2005

  6. Bordone L, Motta MC, Picard F, Robinson A, Jhala US, Apfeld J, McDonagh T, Lemieux M, McBurney M, Szilvasi A, Easlon EJ, Lin SJ, Guarente L. Sirt1 regulates insulin secretion by repressing UCP2 in pancreatic beta cells. PLoS Biol. Feb;4(2):e31, 2



These mechanisms have probably been confirmed in vitro. But there is a long history of things that work in vitro or administered IV that are disappointing with oral delivery. When there is money to be made or lost, there is often no unbiased info from the source drugs or supplements. We need to see some kind of results or data from use of the specific oral compounds.

I don't know what one would test for? At first glance, one would not expect to see any change to T levels. So what blood markers would show effectiveness? And the effect that is sought may also make receptors in the hypothalamus/pituitary more sensitive and the effect might decrease T in vivo. We see this type of thing where SERMs decrease the sensitivity of receptors in the hypothalamus/pituitary which then increases LH and T.

If it works orally, the HPTA feedback may diminish any benefits. Too many unknowns.

Example: Great data in a lot of amino acids to cause GH release. Many of the dose-response studies were with delivery of the amino acids by IV, not oral. And then there ofter were no reports about whether the 24 hour release amounts were the same or increased or any data of GH release changes after sustained use.

A whole industry of amino acid supplements created to increase GH was born with little data to support anything. I have never seen any data where test subjects took anything where IGF-1 levels before and after have been reported, let along long term effects on IGF-1. As long as companies are making money selling these things, why would anyone spend the money to get real data or risk spoiling the game with any data that might kill the industry.


that's pretty interesting. i wonder about side effects from the drugs though?


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I read a few thread where the guy who wrote the article above posted.

He said that although there is a controversy concerning the AR, the vast majority of receptors in the body downregulate.

I also read about a study that showed that the AR upragulated within a few weeks of taking AAS and then returned to normal within 2 months.


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This should explain why...



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Yeah, there's usually tissue specificity with ANY signal transduction pathway, especially hormones. I would also point out that the upregulation that Schwarzenegger posted with the abstract was carried out in TUMOR cells, which are a far cry from any normal tissue. Both their metabolism and signal transduction pathways are screwed up.

In some cases it is true that they show parallel results with normal tissue cultures, and sometimes even hypersensitivity, but it is in no way a generally reliable extrapolation to go from cancerous cells to normal tissue.

It must generally be established via a separate set of published studies that tumor cells of a certain kind are in fact a useful model of some physical phenomena before people are encouraged to speculate.

Very interesting article OP. The refs are in good order and from good journals, and the science seems sound to me. However, I could never venture a guess as to whether the product itself is any good. There is a world of difference between in vitro studies and real life, as already mentioned. Besides we don't know the bioavailability of the ingredients administered.

I suppose you could always order the product and use it to see if one of your previous moderate cycles gives you better results the second time around. That might be experiential evidence. It'd have to be a cycle that you were very familiar with on a physical and emotional (intangible) level to give useful insight.