But if android receptors are upregulated, shouldn’t you get a boost?
Hormones attach themselves to receptors and then unbind in a very short span of time.
If there are more receptors, then the process of binding and unbinding should happen at a higher frequency.
I always thought our problem came from down-regulated receptors and/or lower hormonal level.
No, upregulation does not necessarily mean “a boost”
Part of the mystery of PFS is that we just don’t know why the receptors don’t function properly. I guess I shouldn’t have mentioned upregulation, because that isn’t the cause of them not functionain’t but rather a symptom, a coping mechanism by the body, that points to something else preventing the receptor from working altogether.
I see.
But as some people get better over time, would you say the receptors get “repaired” at least somewhat for some people?
Regarding over-expressed androgen receptor, this is discussed in the admins’ paper
Induced Wild Type AR Overexpression and the potential relevance of SBMA to PFS
As discussed, as the CAG trinucleotide sequence extends in the N-terminal domain of the AR, there is a consequent functional decline in transcriptional efficiency which is seemingly associated with a compensatory increase in androgen levels. However, at longer repeat lengths, high androgen levels can exert a deleterious and ultimately toxic response. Crucially, polyglutamine expansion is not the only way ligand-dependent toxicity can be conferred to the AR protein, and overexpression of the wild type AR can cause a paradoxical loss of function and toxic gain of function. This is reflective of evidence in other polyglutamine diseases that point to gain of native protein function underlying pathology (Paulson et al., 2017). It is now appreciated that balanced gene expression is vital for homeostasis, and overexpression of wild-type proteins causes disease states in humans (Ohshima et al., 2017; Shastry, 1995). Multiple studies demonstrate that, while seemingly paradoxical, sufficient increases in AR expression converge with loss of function phenotypes, with an inverse U‐shaped curve representative of AR gene dose response in tissues. The pathological consequence of overexpression of the AR is therefore coherent with Prelich’s observation that overexpression of proteins mimics a loss of function and interferes with its function antimorphically. The mechanisms by which overexpression causes a mutant phenotype is therefore of great importance to further understand (Prelich, 2012).
Generating mice overexpressing AR solely in skeletal muscle, Monks et al. reported the striking and seemingly counter-intuitive observation that overexpression of the Wild-Type androgen receptor recapitulates the pathological consequence of polyglutamine expansion despite a polyglutamine repeat tract comprised of 22 glutamines. Decreased viability was observed in males of all seven transgene lines but not in females. Interestingly, administration of flutamide to pregnant dams enhanced perinatal survival, suggesting prenatal androgen activation of the overexpressed AR, not the overexpression per se , is causative of death. Two transgenic mouse lines of differing WT AR copy number (L78 < L141) were characterised. L141 males exhibited a far more severe phenotype, corresponding to a significantly higher AR expression at the mRNA and protein level. Surviving L78 males were functionally comparable to wild type despite a lower body weight. However, L141 males exhibited a marked phenotype of lower body weight, curvature of the thoracic spine, severe deficits in motor function and muscle strength, and early death. Castration dramatically restored function in L141 mice, illustrating the androgen dependency of the toxicity. Remarkably, although L141 females were apparently unaffected by AR overexpression per se , when administered testosterone to the approximate circulating level of male mice, they rapidly developed a comparable disease phenotype to male L141 mice including motor dysfunction and muscle atrophy. Over 9 days of T treatment was fatal to female L141 mice. L78 female mice did not become symptomatic or atrophic with T treatment, even for prolonged periods. This parallels the asymptomatic L78 male. This is strongly indicative that the degree of overexpression dictates severity of androgen-mediated toxicity and, as Monks et al. observe in several contexts, that overexpressed AR confers toxicity once activated by hormonal ligand (Monks et al., 2007).
Over the past 3 months, I lost a lot of muscles and I was experiencing tons of muscle and bone pain (most likely deterioration). The pain is now gone, except for some slight pressure on my back from time-to-time. My penis is no longer shriveled when flaccid. I no longer get numbness in my hands.
Would you say one possible explanation is that my AR receptors were over-expressed in the first couple of months and now they’re getting less dense?
You did not understand what I said to you. How expressed or dense the ARs likely has nothing directly to do with PFS itself. It’s a coping mechanism done by the body because the androgen receptors themselves do not work.
Stop thinking about AR “expression” or “density”, because with PFS the ARs themselves do not work, so the number of them does not matter.
???
Tzinkman’s article talks about AR overexpression in rats and the inverse U-shaped effect.
Nowhere does he say that’s the cause of PFS. The point of the study was to investigate the effect, which is good. But doesn’t mean it’s what’s causing PFS.
So how are you so sure that “damaged receptors” are what’s causing PFS?
Well, I can’t be so sure truthfully, because there’s no hard studies on it yet, but based on the upregulation of them and increase in density that is my hypothesis.
I’ve noticed a lot of improvements with some of my symptoms.
In your view, would it be possible for receptors to be repaired at least somewhat for some people?
Yeah, they could be. Especially with human growth hormone. Look into that.
But for some people, make no doubt this is a persistent condition that can not improve for upwards of 20 years,
hi, guys,
I’ve had a very stressful week at work. The truth is that I’m having a hard time keeping my job (I’ve been at it since February and not being able to leave work…I think the stress might make it difficult for me to recover)
What I’ve noticed this week:
What do you recommend? I had thought of buying collagen peptides, BCAA and do not know if to include some supplement that enhances growth hormone.
Tomorrow I’m going to do the first post-finasteride tests. I prefer that there be a hormonal alteration so that these symptoms can be explained. The endocrinologist told me I might have hypogonadism
I would say the time is the best healer in the beginning and implementing supplements so early can miss out the time as a healing factor.
Are you still using oral minoxidil? Minoxidil is known for causing wrinkles and dry skin
Ask your endocrinologist to prove his hypogonadism theory by doing labs. As victims of this drug that poisoned us, we need absolute proof, and that can come by way of lab results. Hopefully, what affected us is detectable and measurable, otherwise we won’t be believed.
Hi, guys.
I come to you with news. I finally got results for my blood test. It is still pending confirmation of DHEA and DHT levels. But so far I have obtained something very interesting.
In view of this I would appreciate it if you could help me see what has happened in my body
Pre Finasteride Test:
TSH 1.02
FREE T4 1.09
Testosterone 7.04
Post Finasteride test:
FSH 4.04 mUI/ml (1.5 - 12.4)
LH 5.88 mUI/ml (1.7 - 8.6)
17-Beta estradiol 51.60 pg/ml (11.3 - 43.2) ***
Progesterone 0.35 ng/ml (0.05 - 0.149)
Prolactin 9.69 ng/ml (4.04 - 15.2)
Intact Parathormone 46.60 pg/ml (15 - 65)
Testosterone 8.08 ng/ml (2.49 - 8.36)
Free Testosterone 130.10 pg/ml (54.7 - 190.63)
Delta-4 Androstendiona 2.23 ng/ml (0.6 - 3.1)
ACTH 22.40 pg/ml (7.2 - 63.3)
cortisol 14.00 ug/dL (4.82 - 19)
25-HIDROXI VITAMINE D 15 ng/mL ( >30)
HDL Cholesterol 50 mg/dl ( >55)
Hydroxyprogesterone 17-alpha
IGF-I (Somatomedin C) 162.00 ng/ml (109 - 257)
Insulin 5.62 µI/ml (2.6 - 24.9)
Serum SHBG (Sex hormone 50.30 nmol/l (18.3 - 54.1)
binding globulin)
Thyroid Profile
Anti Microsomal TPO <9 IU/ml (Inf. 34) Negative
TSH 0.87 µUI/ml (0.4 - 4.5)
Free T4 1.16 (0.7 -1.9)
Anti Thyroglobulin (TG) 10.90 IU/ml (Inf. 115) Negative
High levels of progesterone (x3), estradiol, low vitamin D and HDL and testosterone slightly higher than before starting finasteride
What do you think? Are they typical of pfs?
After seeing my blood tests my IGF1 values seem normal. I really don’t know what steps to take from now on.
I would like to at least regain the elasticity of the skin and the loss of subcutaneous fat in the face. I have especially dry and wrinkled skin on my hands and feet since I left finasteride.
Do you recommend it in my case too? I’m having a very bad time and lately I’m only thinking of killing myself.
I got news for you guys.
I was with an endocrinologist yesterday who specializes in PFS. He recommended me to start with a treatment to be able to revert the symptoms, however I don’t trust it completely and reading experiences of the forum I don’t know if this will be a good treatment. The treatment would consist of testosterone injections every 21 days (but I don’t think that’s reliable knowing that I have high testosterone)
The regime would be:
Tamoxifen 20mg daily
cialis 5mg daily
bupropion 150mg
I’m actually quite doubtful about the treatment. I think it’s been a short time since I left treatment and I don’t know if this could make things worse. I told the doctor several times that I didn’t understand about injecting testosterone with high levels…
Your test is already near the upper range. What is the point of getting the test shot?
I don’t understand it very well either. He told me that the idea was to reverse the whole process “backwards”. I’m going to ask for a second opinion, since I see that it’s quite far from the stories I’ve read in the forum. In other words, it would be better to wait for the moment.
I got another blood test result today and of course it is also wrong … it gives me a very high value. The worst thing of all that in my case the endocrines do not know how to interpret it
Hydroxyprogesterone 17-alpha: 2.61 (0.05-1.6)