(1)Testosterone down-regulates the levels of androgen receptor mRNA in smooth muscle cells from the rat corpora cavernosa via aromatization to estrogens.
ncbi.nlm.nih.gov/pubmed/8499343
(2)Up-regulation of the levels of androgen receptor and its mRNA by androgens in smooth-muscle cells from rat penis.
ncbi.nlm.nih.gov/pubmed/8495802
To summarize the first study, (1) indicates that AR could become downregulated even before stopping fin and suffering the PFS “crash”. While these studies should be taken with a grain of salt because they are focused on rat penises, rats in (1) experienced a downregulation of AR expression due to increased estrogen levels caused by fin administration (fin blocked T conversion to DHT, therefore excess T aromatizes). However, counter to the researchers’ hypothesis in the second study, (2), that increased androgen levels would downregulate AR, DHT increased AR expression after androgen deprivation. To me, these two studies indicate that there are 3 possible mechanisms by which AR expression changes due to fin use, with any combination of the 3 being the actual cause:
- Increased estrogens while on fin
- Decreased DHT while on fin
- Extreme DHT surge upon cessation of fin (vs. a moderate increase in DHT which can upregulate AR expression and not suppress the HPTA)
Why would some benefit from proviron and not others? Is it possible that those who do not respond to TRT, proviron, or androgen supplementation at all have the highest rate of AR downregulation? Supplementation with carnitine has been shown to lower circulating free testosterone levels because carnitine increases the uptake of the free testosterone. If due to decreased AR expression, a person can’t absorb high levels of artificially circulating androgens, then his body would possibly respond by shutting down endogenous production (i.e. ingest proviron —> body senses way too much DHT —> shuts down T production —> bodily process dependent on T, but not DHT suffer). So, the trick would be taking in the amount of proviron/DHT that is suitable for one’s current level of AR downregulation, then slowly increasing proviron/DHT intake to match increases in AR expression. Would this be incredibly hard to do? Absolutely. Is it impossible to do? Maybe not.
The practical problem would be the need for consistent measurement of circulating androgens. As AR expression increased, circulating androgen levels would decrease due to greater uptake by the body. When circulating levels have decreased, one would increase proviron/DHT uptake to further increase AR expression, repeating this process until stable.
LH and FSH would need to be measured in order to ensure that the decrease in circulating androgens is due to increased AR expression and not negative HPTA feedback. If LH and FSH increase or stay the same, and circulating levels of T and DHT decrease, then increased AR expression can be assumed (good). If T and DHT decrease, but LH and FSH also decrease, then negative feedback is occurring and endogenous production is shutting down (bad). Is it possible, that using this methodology, a person could selectively modify AR gene expression without risking body-wide demethylization? I believe so, but I’m not a scientist or medical professional, so please do not take anything I’ve said as medical (or even sound) advice.
Please let me know if this idea makes sense and/or should be in an individual thread.
Take care,
Former