To facilitate your discussion, I am offering an excerpt from a paper which I have co-authored (currently unpublished). You will find a bit on AR signaling pathways and more importantly, gene regulation. Perhaps this will help appreciate the fact that the body actually has its own mechanisms to deactivate the AR (or rather, its signaling).
AR_Signaling_Overview.pdf (605 KB)
Awor this is extremly interesting. You are a very smart man, keep up the good work
http://www.endotext.org/male/male2/maleframe2.htm
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(77)91825-6/abstract
Thanks for the back up bro 
youtube.com/watch?v=N1t2QYdx … re=related
Awor, the way the body deactivates/down regulates AR is by dumping zinc?
The body can downregulate or even deactivate the AR signal by a number of means. To illustrate this, one first has to understand what happens when androgen hormones (called ligands) “mate” with the androgen receptor:
- Ligand binds to AR
- AR travels to cell nucleus and triggers transcription (copying) of AR target genes to a copy of those genes called “RNA”
- RNA then travels to a structure within the cell called a ribosome. The ribosome reads the “message” (RNA) and produces a correponding protein. This is called translation.
- This protein often must undergo a finishing step called “posttranslational modification” before it reaches its final, active form. The fully functional protein is what is called a “signal”, because it signals other mechanisms/cells to do something.
- The finished protein (=signal) is what makes androgenic things happen such as keeping the penile structure intact and muscle cells growing, helps give us an erection, helps in producing sperm, keeps our prostate healthy, gives us libido, etc.
So to answer your question, the body “silences” the AR signal mainly by either downregulating step 2 (making less copies of RNA) or step 4 (by modifying the protein in such a way that it’s basically useless = posttranslational modification). Posttranslational modification is actually the most prominent mechanism the AR has at its disposal to completely silence the AR signal if required.
A number of substances can either inhibit or promote transcriptional activity (step 2). Zinc seems to have an effect on transcriptional activity by potentiating AR binding to nuclei [1], which basically means that it increases transcription. This effect could be due to the upregulation of one of the many modulators of transcriptional activity. But the body doesn’t directly influence zinc levels to regulate the AR to my knowledge. That would be an odd way to go about things.
Awor, any insight into why only the select few get screwed.
-Because i lied when i was 17?
-Purposely stepped on bugs?
Seriously do you have any theory on this?
There undoubtedly is something at the genetic level which makes us different from the “rest”. See my thoughts on this in following thread: viewtopic.php?f=27&t=4296&p=28089#p28089
I am also pretty sure that our group on this forum is just the tip of the iceberg. If you observe the reports from sufferers around here, you will notice that even amongst us, there is a huge disparity of how severely everyone is affected. If you extrapolate this observation, it is plausible that there may be many guys out there that have side effects, but to a even lesser degree than “we” (perhaps mild forms of ED, a little less libido, small concentration problems, etc.). If the incurred changes are subtle enough, it is easy to imagine that the affected men will not put them in relation with the drug. It is also very possible that not everyone has found us yet, perhaps because they are older and not Internet savvy. We all know that they won’t get our address from any doctors…
The idea that everyone here was genetically predisposed to this disease would only be borne out
if all of us had taken fin for a few months at most and crashed after coming off the first time.
I myself, like quite a few others here, took the stuff for a long time with breaks sometimes
where no crash occurred, in fact I returned to normal. Ok I had sides most of the time but
they were the relatively minor ones awor describes.
It was only the last run of fin that nailed me, and maybe if I’d paid attention to sides earlier or
quit by weening off I could have avoided problems. Maybe just bad lifestyle helped nail me.
If there is a genetic predisposition perhaps that would apply to potentially everyone who gets
sides, which is probably 15-20% at least.
I also wonder why there are no older guys who used it for BPH etc posting, seeing as many 45+
guys who used it for hairloss are here, and I’ve seen accounts elsewhere on the web of older guys
having bad ED from proscar.
I found out that now the Gastrin Releasing Peptide receptors are now known as Bombesin (BB2) receptors for whatever reason…Can anyone find any way to stimulate (agonize?) the BB2/GRP receptors?
I found this link ncbi.nlm.nih.gov/pubmed/18488022
Abstract
Neurons in the upper lumbar spinal cord project axons containing gastrin-releasing peptide (GRP) to innervate lower lumbar regions controlling erection and ejaculation. This system is vestigial in female rats and in males with genetic dysfunction of androgen receptors, but in male rats, pharmacological stimulation of spinal GRP receptors restores penile reflexes and ejaculation after castration. GRP offers new avenues for understanding potential therapeutic approaches to masculine reproductive dysfunction.
No one seems to be giving this Gastrin Releasing Peptide much attention. I found some at Pheonix Pharmaceuticals for $90 Im gonna get some I guess …
I had the same experience – breaks but the last hurrah screwed me.
On the issue of weening off (i didnt…i stopped cold turkey), many are stating that cold turkey is better. See a little discussion on that here
Good question. Though I’ve seen older guys who used it for bph posting on other sites. When you’re that old, you almost accept that your libido is on the downside, and most docs will attribute ED/shrunk junk/low T to age.
VERY VERY interesting. Thank you!!
okay I will buy it. and I’ll try it. but can someone help me figure out how much to take??? i dont want to die
bump
ncbi.nlm.nih.gov/pubmed/19359382
Endocrinology. 2009 Aug;150(8):3672-9. Epub 2009 Apr 9.
Androgen regulates the sexually dimorphic gastrin-releasing peptide system in the lumbar spinal cord that mediates male sexual function.
Sakamoto H, Takanami K, Zuloaga DG, Matsuda K, Jordan CL, Breedlove SM, Kawata M.
Source
Department of Anatomy and Neurobiology, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. hsakomo@uml.okayama-u.ac.jp
Abstract
A collection of neurons in the upper lumbar spinal cord of male rats projects to the lower lumbar spinal cord, releasing gastrin-releasing peptide (GRP) onto somatic and autonomic centers known to regulate male sexual reflexes such as erection and ejaculation. Because these reflexes are androgen dependent, we asked whether manipulating levels of androgen in adult rats would affect GRP expression in this spinal center. We found that castration resulted, 28 d later, in a profound decrease in the expression of GRP in the spinal cord, as reflected in immunocytochemistry and competitive ELISA for the protein as well as real-time quantitative PCR for the transcript. These effects were prevented if the castrates were treated with testosterone propionate. Genetically male (XY) rats with the dysfunctional testicular feminization allele for the androgen receptor (AR) displayed GRP mRNA and protein levels in the spinal cord similar to those of females, indicating that androgen normally maintains the system through AR. We saw no effect of castration or the testicular feminization allele on expression of the receptor for GRP in the spinal cord, but castration did reduce expression of AR transcripts within the spinal cord as revealed by real-time quantitative PCR and Western blots. Taken together, these results suggest that androgen signaling plays a pivotal role in the regulation of GRP expression in male lumbar spinal cord. A greater understanding of how androgen modulates the spinal GRP system might lead to new therapeutic approaches to male sexual dysfunction.
so have you tried it?
I haven’t because of the dosage. U can buy one mg. So I was thinking take a mcg. But then I read about one nanogram! And that scared me because I was so far off… there’s also like 10 kinds u can buy at pheonix pharmecueticals and I don’t know which one to get. I also read about how gastrin can progress cancer so I def don’t wanna take too much and how it can cause instant ejaculation so it seems like it would b stupid to take it blindly…
Any assistance with this would b great!
I doubt anybody here could help you with that
The best would be to contact the authors of that study (ncbi.nlm.nih.gov/pubmed/18488022) and ask them about what they think the optimal dose of GRP would be for treating rats with impaired sexual function, and what would be the best protocol to use for its administration… Also ask them about the different gastrin peptides and which one would be appropriate. Off course you should come up with a story, prentending you are a doctor or some student doing a research on the subject. Or maybe just purchase the whole article since all these answers are probably in there.
Then you could try to convert the “rat dose” into “human dose” using this fasebj.org/content/22/3/659.full.pdf (“Dose translation from animal to human studies
revisited”)
As the abstract states, “The animal dose should not be extrapolated to a human equivalent dose (HED) by a simple conversion based on body weight…” The FDA has stated that the extrapolation of animal dose to human dose is correctly performed only through normalization to body surface area. To convert mg/kg in rats to mg/kg in humans, you multiply by 0.162 (6/37). For mice to humans, multiply by 0.081 (3/37). There are several other values for other animals.
Please keep us posted!
Thank you! Great post…
I was wondering though about the conversion. You say you would multiply the dose given to the rat by a decimal. This would result in a lower dose than given to a mouse. Are you sure you dont DIVIDE by that number which would increase the dose. Or are you saying you need to take less as a human than you would give a mouse?
how could finasteride cause a condition like this though?
We should also look at DHT in the prostate…