I found this report and I thought it will be a good idea to share it with all of my friends here:
[[While it would have been unthinkable to give T to men with PCa not too many years ago, this is part of the cutting edge research currently in progress. An in vitro study showed that supraphysiological androgen levels induce cellular senescence in human prostate cancer cells [38]. The researchers used R1881, an androgen which cannot be converted to estrogen. This demonstrated that senescence was caused by androgen receptors and not estrogen receptors. Phase 1 trials were done in which T was administered to men with early-stage CRPC. In one study of 15 men, one patient showed symptomatic progression and three patients experienced drops in their PSA [39].
The study concluded that high dose exogenous T could be safely administered. Another similar study came to the same conclusion, with 7 out of 12 patients observing some drop in PSA, although many of the patients were treated with different doses of T and for different durations [40]. A different study analyzed the effect of T on men with low T and early-stage PCa that had no previous treatments performed. If T fueled PCa, then some of the patients should have experienced rapidly growing PCa, but none did. In fact, the 13 men who were treated for an average of 3.1 years had an average decrease in their PSA by over 33% [41].
These experiments demonstrated that the old beliefs about T were wrong, but they did not point the way to how T might be used as a treatment option. The most important thing to consider when using T therapeutically is that there must be a relative balance between the iAR and the membrane androgen receptor (mAR) in order for PCa to grow [42]. This is because mAR downregulates AS3, upregulates bcl-2 but upregulates proapoptotic proteins even more, with T and DHT binding equally well to mAR. Apoptosis occurs in the presence of mAR agonism with no iAR agonism [42]. On the other hand, iAR upregulates AS3 and downregulates bcl-2 as well as the proapoptotic proteins upregulated by mAR [14].
This means that if there is iAR agonism with no mAR agonism, then, in theory, the PCa should be unable to proliferate. In practice, when the LNCaP cell line was modified to have the ability to grow in very low levels of androgen, it resulted in the amplification of iAR by at least 10-fold. This new cell line, named LNCaP 104-R2, could not grow in the presence of T, but could grow in the presence of T plus finasteride [43]. Finasteride is a drug that inhibits 5-reductase (5AR) type 2, which is an enzyme that converts T to 5-dihydrotestosterone (DHT). In the prostate cell, T is almost always converted to DHT by 5AR type 2 and DHT binds to iAR approximately 5 times more strongly than T does [14]. Therefore, even though there is some agonism of T to mAR, with T and DHT having equal agonism to mAR [42], there is much more agonism to iAR because of its amplified number. This imbalance results in mitosis being prevented, presumably because sufficient AS3 is being upregulated. When finasteride is added to prevent the conversion of T to DHT, this reduces the agonism to iAR 5-fold. Although there is still more agonism than normal of iAR as compared to mAR, this is not enough to prevent mitosis.]]
Friedman - DHT, etc..
