What could we do to test those levels or function?
I somehow have the impression that all the studies are taking too much time in a way. Or they might not research the right target.
I dont believe anymore in those studies and help. My personal opinion.
Cause if we found forex the root of depression and ED, who will by AD or ED drugs? Who? NOBODY. This is a huge market. So, for me it is clear: Pharma won’t allow finding the root.
You can call me idiot or no sayer. But the thing is: a lot of ppl didn’t believe me in lots of situations, but admitted later I was right.
Just thing about my lines what a cure! (the root and treatment) of lots of symptoms Pharma is making huge money with it would mean for those companies? If you have the key to cure depression and impotence, you are concurrence to pharma. Do you really think they will allow that?
I really thought I stumbled upon something significant until finding out that EGR1 seems to mainly promote survival and growth of androgenic tissue in the absence/deficiency of androgens. …It does not appear to be directly involved in modulating sensitivity to androgens by promoting overexpression of the AR, as would be expected of a gene/protein involved in PFS. Though, it could achieve reduction in the transcription of androgen-activated genes by reducing the positive effect SP1 has on activation of AR-target genes. That might sound like a confusing mess, but what is important is that EGR1 alone is not sufficient to cause AR overexpression. I would need to know more before commenting further.
If anything, it is likely to be a simple marker of an anti-androgenic effect of these drugs. This is also assuming serotonin (SSRIs) and Accutane don’t increase EGR-1 expression via a different mechanism that has nothing to do with an anti-androgenic effect.
A biopsy would need to be taken from affected tissue and our EGR1 levels would need to be compared against the same tissue in a control group. This ain’t gonna happen.
The pharmaceutical industry can’t possibly be that evil or powerful, right?
Excerpt from interview with the discoverer of H. pylori as cause of stomach ulcers :
That letter must have provoked an uproar.
It didn’t. In fact, our letters were so weird that they almost didn’t get published. By then I was working at a hospital in Fremantle, biopsying every patient who came through the door. I was getting all these patients and couldn’t keep tabs on them, so I tapped all the drug companies to request research funding for a computer. They all wrote back saying how difficult times were and they didn’t have any research money. But they were making a billion dollars a year for the antacid drug Zantac and another billion for Tagamet. You could make a patient feel better by removing the acid. Treated, most patients didn’t die from their ulcer and didn’t need surgery, so it was worth $100 a month per patient, a hell of a lot of money in those days. In America in the 1980s, 2 to 4 percent of the population had Tagamet tablets in their pocket. There was no incentive to find a cure.
Nearly everyone on this site can understand your negativity, but repeating it endlessly does no good in any way.
If you read that article I linked, you’ll see that the good guys, and the public, won eventually.
Re pharma: having the solution for ED and Depression is a danger for them.
Depression are linked to gut issues and heavy metal load there and in brain, but no doc treats that with supps, detoxing, infusions etc.
And the information are not widespread.
But if you present a real cure by targeting genetics or epigenetic modulation, who will earn money with depression, ED, ADHD?
This sector is worth billions of dollars.
You might not be aware of the power of Big pharma, but it is ultimate as in other sectors.
So, no scientist will be doing anything without permission of Pharma.
BTW, I am not quite sure why they want to treat us this way. How would they react if we did behave like them? They would hate us I guess.
I am bringing the joke regurarely: when I have enough seen on this earth, I am going back and sending an asteroid to the earth in order to restart and rebalance the actual state. This is my present.
I read you can order some asteroids from Planet XY on amazon via express delivery
I somehow feel unfort. I have enough seen here on that planet :)
I will follow my order.
Interesting post dubya, thanks. So, mRNA levels of EGR1 are appreciably increased by all anti-androgen drugs mentioned, and SSRIs. This indeed seems like a consequence as you say and, along the line of thought you are pursuing, would likely follow from the impairment of the androgen pathway in “PFS”.
In terms of an initial relevant anti-androgenic effect from the SSRI class: There is suggestive evidence that could support the same mechanistic etiology as PFS/PAS (ie sharp reduction of androgens) via upregulation of 3α-HSD and 17β-HSD. Both enzymes are responsible for the synthesis of key neurosteroids, but importantly reduce DHT to androgen metabolites (5α-androstane-3α,17β-diol and 5α-androstane-3,17-dione) which are metabolites that are controversially either inactive or substantially weaker as AR ligand. In particular, by deactivating androgens, 3α-HSDs determine the amount and the type of androgen available for the androgen receptor and hence affect transcription of genes subject to androgenic regulation.
Research has shown that SSRI class medications such as fluoxetine and paroxetine induce a 63 to 163 fold upregulation of 3α-HSD and 17β-HSD activity (Griffin LD, 1999). The upregulation of these androgen reducing enzymes will lead to a significant reduction in DHT at the cellular level. As such, from the point of view of the androgen receptor, the inhibition of 5AR and upgregulation of 3α-HSD/17β-HSD activity have a common effect: A considerable reduction the amount and potency of available ligand. This effect on 3α-HSD mRNA expressions, mediatory of the reduction of 5α-dihydroprogesterone to allopregnanolone, would explain the often mentioned neurosteroidogenic effect associated with this drug class.
I don’t understand. So SSRIs increase neurosteroids that are decreased with fin use? Wouldn’t their use provide temporary relief of mental sides and insomnia? But their pathways to generating neurosteroid reduces DHT in cells significantly, but how persistently? So ultimately taking SSRIs or other drugs that similarly stimulate the same serotonergic receptors could contribute to worsening of PFS symptoms across the board including mental sides and sleep sides?
And if something induces 5alpha-R gene expression, does it mean it’s inhibiting 5AR and inducing some compensatory mechanism in the body that’s redolent of finasteride’s inhibitory effects?
How do drugs like trazodone (SARI) fit into this picture? Would it have the same result of significant reduction in DHT? What would it mean in terms of sleep?
“Although its mechanism of action is not fully understood, the main pharmacological action of trazodone is blockade of the serotonin 5-HT2A receptor (1mg of trazodone roughly blocked half of brain 5-HT2A receptors)”
“Unlike SSRIs, TDZ simultaneously inhibits serotonin transporter (SERT), while acting as a partial serotonin 5-HT1A receptor (5-HTR) agonist and a 5-HT2AR and 5-HT2CR antagonists”
I’ve been taking Trazodone 25mg and it stopped working on the third night. As someone who’s suffered from chronic severe insomnia before fin, I’m desperate. But I’ve been warned about possible worsening of PFS so now I’m afraid to take any more. Is there nothing safe pharmaceutical wise or AD-wise to take for someone whose natural sleep pressure has been demolished?
"Identification of Genetic Pathways Activated by the Androgen Receptor during the Induction of Proliferation in the Ventral Prostate Gland"
Furthermore, early growth response-1 (Egr1) RNA levels were reduced. Egr-1 is typically an anti-proliferative, pro-apoptotic protein that, in certain cell types functions by activating p53 expression(37). These data are consistent with AR repressing p53 function indirectly by altering the expression of its key regulators.
But they cite EGR1 as belonging to a pro-apoptic pathway. Rather than promoting growth of prostate cancer cells despite androgen deprivation, it is more likely that it is increased as an apoptic signal due to the lack of androgens, while its pro-apoptic signalling through p53 fails for some other reason.
The question of EGR1 increase being specific to an anti-androgenic effect remains. e.g.: Would it also be increased in breast tissue as an apoptic signal resulting from low estrogen levels?
A Master’s thesis containing a nice summary about AR - EGR1 interactions in prostate cancer:
The Identification and Study of Transcription factors and cofactors other than androgen receptor that could have important role in the regulation of gene expression in prostate tumor:
Gene Location: Chromosome 5 , Band: 5q31.2
EGR1 (Early Growth Response - 1) is a transcriptional regulator associated with the activation of cell differentiation and mitosis trigger (Guerquin et al., 2013) (Zwang et al., 2011) . In prostate cancer, EGR1 has the dual role of both suppressing and progressing tumorigenesis . It is involved in apoptosis and cell growth. EGR1 is present in high concentration (Thigpen et al., 1996) in the tumor cells than in normal cells due to the mutational loss of its repressor NAB2 (Abdulkadir et al., 2001) or mutation of B - RAF gene (Davies et al., 2002) . In a hormone - dependent environment, EGR1 interacts with cascading to a series of events from AR translocation to nucleus, transcription of PSA (Prostate - Specific Antigen) and finally to tumor proliferation (S. Yang, 2003) . In hormone - independent situation, EGR1 in overexpressed levels enhances the prostate cell growth by interacting with the low AR levels and downregulating AR target genes (Mulholland et al., 2011) (S. - Z. Yang, Eltoum, & Abdulkadir, 2005) . Inhibition of EGR1 leads to blocking the metastasis of tumor cells (Mulholland et al., 2011) . Hence EGR1 is a potential target for anti-cancer therapy.
Life experience can leave lasting marks, such as epigenetic changes, in the brain. How life experience is translated into storable epigenetic information remains largely unknown. With unbiased data-driven approaches, we predicted that Egr1 , a transcription factor important for memory formation, plays an essential role in brain epigenetic programming. We performed EGR1 ChIP-seq and validated thousands of EGR1 binding sites with methylation patterns established during postnatal brain development. More specifically, these EGR1 binding sites become hypomethylated in mature neurons but remain heavily methylated in glia. We further demonstrated that EGR1 recruits a DNA demethylase TET1 to remove the methylation marks and activate downstream genes. The frontal cortices from the knockout mice lacking Egr1 or Tet1 share strikingly similar profiles in both gene expression and DNA methylation. In summary, our study reveals EGR1 programs the brain methylome together with TET1 providing new insight into how life experience may shape the brain methylome.