The first way is: Once you are on ADT, your T levels fall much faster than your PSA levels. Should they not fall together? T triggers the synthesis of PSA. If T in the blood collapses, should not the PSA synthesis that was previously triggered by T stop at the same time, rather than some later time?
A second way to ask the same question is: what happens to an activated AR after it binds to the DNA and the mRNA for PSA synthesis leaves the nucleus? Does it continue to sit on the DNA and generate another mRNA? And what happens to the mRNA after the ribosome finishes synthesizing the PSA?
I’m waiting to see who replies to “the second way”. The first is my question as you may know. T of 14 and PSA spiking to 188? I doubt this combination of low/high will ever make sense; your “second way” to ask the question may be part of my answer.
Maybe Monday we will learn if Zytiga for three weeks has brought down his PSA. Would it further bring down the T? I want it to go up—primarily for good health, you understand. Mrs. S
P.S. Why not one pill instead of four but taken with food to lower costs? 6 billion less for Janssen must be the answer to that one. sciencedaily.com/releases/2...
You misunderstand the biochemistry. PSA is NOT synthesized directly by T or any other androgen as you seem to imagine. PSA - prostate specific antigen- is a protein generated by ALL prostate cells, cancer or not. PSA rises in direct proportion to the NUMBER of prostate cells. If you were to take even a small amount of prostate tissue and put it in a blender, the PSA would be astronomically high. However, PSA is only detected in the SERUM if there is a structural problem with the prostate cells, such as BPH, prostatitis, prostate cancer, or mechanical breakage. Prostate TUMORS generate their own blood supply, but the blood vessels are somewhat leaky. Consequently, their PSA leaks out into the serum where it is detectable. Very small metastases do not have their blood supply yet, so their detected PSA is minuscule. Testosterone activates the AR, which encourages cell division and growth. So the more T, the larger the tumor, the more PSA will eventually be detected.
Very kool comments my friend, you might need to be on lab oversight committee. THEY, don't know half of everything bro, most is a guess, although they're are many outside of the USA, that have a much better view with factual proof on hand. Let that sink in a bit.
PSA is a proxy for cancer. It is NOT cancer. Serum PSA rises from a number of causes other than cancer.
Once RP or RT has removed or destroyed the prostate gland, then any remaining PSA is probably coming from metastases, which is why men without their prostates worry about PSA readings much less than 4, while men with prostates start worrying at higher levels.
Even when there is a strong link between PSA readings and T readings, they are not in lockstep. There is a lag, for example, between the large increase in T used in BAT and the rise in PSA. As Nalakrats points out, some men on BAT see PSA fall when T is very high.
Once castration resistant prostate cancer develops, the link between PSA and T is even more tenuous.
Your last paragraph may be our problem in a nutshell. Excellent. Thank you for your persistence and not giving up on any of us—even those as confused as I am. I enjoy reading all of you.
The BAT results above are fascinating. I also agree that low T as a result of aging could be causative of APC which would explain why approximately 80 per cent of (male obviously) 80-yr-olds have the disease.
FYI, we decided to continue with dutasteride and finasteride while on abiraterone even though some on this site think it is unnecessary. Who knows that they don’t prevent some lethal conversion of T to DHT and E2? Mrs. S
1) I am not talking about BAT. It would be nice to know why the PSA level goes down for some even when T levels are high, but that is not the case that I am asking about. I admit that the Testosterone story in this case seems incomplete here as well, but that is not a surprise. There is a lot we don't know about BAT.
2) The surpise, for me, is in the decades old use of ADT on initial treatment. The story there has some flaws it seems to me in the simplest case of metastatic but hormone sensitive PC.
The story goes that PSA is synthesized when the AR binds to the DNA and a transcription event takes place. The AR enters the nucleus when activated by T. Each of the steps is a one to one event. One PSA protein comes from one transcription which comes from one T molecule activating one AR. So one protein molecule of PSA comes from one molecule of Testosterone. The labs values should decline in lock step, if that understanding is true, in direct proportion. But they don't. In fact, after the bottom has dropped out of T, the PSA is still gently floating down. How is it being synthesized, and why does that mechanism for synthesis come to a stop?
I do understand that these biochemical processes take place in cells that are cancerous as well as cells that are not cancerous.
I'll try to simplify my explanation. PSA DETECTED in the SERUM is NOT in a one-to-one relation with pSA PRODUCED by the CANCER. They are associated, of course, but not all cancer cells contribute PSA to the serum.
The "argument" does not depend on the number of cells that synthesize PSA.
PSA is not normally destined for blood vessels; it is destined for the urethra. With prostate cancer, a fraction of the PSA gets into the blood by some mechanism, possibly by vascularization of the tumor, or loss of integrity of the enclosing membrane, or whatever. Call this leakage.
If T is dropping, one might argue that the since the PSA concentration inside the gland is higher than the PSA concentration outside the gland (for example, It is 100% higher, roughly, in the case of a healthy prostate), that it is the continuing leakage of PSA from a high concentration to a low concentration that is delaying the collapse of the PSA in the blood. If this is the case, no new PSA is getting synthesized; instead previously synthesized PSA is draining out, and countering the natural clearance rate of PSA from the blood.
If this is the case, then the BAT trials might shed some light, because the particiant's prostate, prior to the BAT therapy, has a prostate that is an "empty reservoir".
So one would be justified in hoping that the PSA collapse post BAT failure (ie for those whose PSA continues to rise), would be faster that their PSA collapse post ADT. Certainly one would hope that the PSA collapse post BAT would not be slower than after ADT, if the leakage mechanism remained the same, ... maybe.
If what I replied did not answer your question, it apparently doesn't make sense to me. But others might understand better than I do what you're getting at.
OK. Here is one thing I didn't get from your first post:
"Prostate TUMORS generate their own blood supply, but the blood vessels are somewhat leaky."
What does that mean? Healthy blood vessels "leak"; stuff normally goes into, and out of, blood vessels. They are not impermeable tubes. Or do you mean that these blood vessels are extra leaky, and that extra leakiness is important in some way? Does the PSA go into, or out of, the blood vessels through the extra leaks? I think you are saying the PSA goes into the blood (mostly??) because of the extra leakiness? If those blood vessels were healthy, the PSA wouldn't get in(?). Or as much(?).
Tumor blood vessels are not well formed as healthy blood vessels are, so they leak out into the serum. That's why a PSA test of the serum detects prostate cancer. Healthy blood vessels do not leak, and no PSA is detected in the serum of men with completely healthy prostates.
Under ADT for hormone sensitive prostate cancer, PSA blood level drifts down slowly even though Testosterone blood level collapses dramatically. The new idea is that the source of the PSA in the blood (those PSA proteins) is not newly synthesized PSA, but is instead PSA previously synthesized and stored in the prostate interior space. That means that nothing of biological relevance is changing or progressing during that gradual PSA blood level collapse to nadir. All that is happening is a slow leaking of PSA out of the prostate.
They say that bicycle riding can raise your PSA, and other things can as well. It is possible that this elevation in PSA is caused by compression of the prostate, causing an acceleration of the diffusion of PSA from the prostate into the blood. Something like this could cause fluctuations of blood serum PSA levels.
Assuming all this is a correct understanding in the case of androgen sensitive prostate cancer, then it seems that, after ADT, stimulation of the prostate, to increase the rate of diffusion, would lead to a faster nadir, and a quicker understanding of whether your cancer is all androgen sensitive, or whether there is a castrate-resistant component.
What would be the best way to do this - to increase the rate of diffusion - to empty the prostate of stored PSA? Some kind of massage, but anything more specific?
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