Let’s say that AR is the problem, then what is going to be the treatment ?
AR activator ?
Any other idea ?
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maybe we shouldnt put our energy into this kind of questions. Im sure you wont find out the exactly mechanism without any scientific background. maybe you have this background but you dont even have any data that you can analyze. so whats the point in asking questions like “is it the AR ?” “Is the problem within the dht receptor?” “I think PFS is endocrine disruption”. Thinking is nice but knowing and proving is way better. dont want to be harsh to you because were all in the same boat and should hold together. but can you please take your energy to fill in the survey instead ? thank you !
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Neural androgen receptor regulation: Effects of androgen and antiandrogen
Androgens exert profound effects on the organization and function of the central nervous system. These effects are mediated by the androgen receptor (AR), a ligand‐dependent transcription factor. The mechanisms of AR regulation in neural tissue, however, remain to be fully elucidated. Characterizing this process can provide important information regarding receptor function and AR gene regulation in the brain. Previously, it was shown that testosterone (T) up‐regulated neural AR in a dose‐dependent manner in both male and female mice. In the present study, whether AR was differentially regulated by the natural agonists T and dihydrotestosterone (DHT) or the nonsteroidal antagonist flutamide (FLU) was assessed. Males were gonadectomized and AR levels were allowed to decline to baseline 3 days after surgery. Changes in AR protein content produced by the various treatments were measured by semiquantitative Western blot of limbic system extracts. Treatment with T or DHT significantly augmented AR 3 and 7 h after hormone administration, but only DHT sustained this increase for 21 h. This difference also was observed when males were given T plus finasteride (FIN, a 5α reductase inhibitor). The findings demonstrate that the two endogenous ligands have differential time course effects on neural AR. The antiandrogen FLU failed to up‐regulate AR at doses up to 100 times higher than T or DHT. When administered concomitantly with T or DHT, it effectively inhibited the augmentation of AR normally seen 3 h after androgen treatment. While immunohistochemical studies showed that FLU was able to promote nuclear translocation of AR, Western analysis revealed that FLU, in contrast to T and DHT, failed to maintain the integrity of AR. The results demonstrate that (a) the endogenous androgens T and DHT regulate AR differently, suggesting a potential cellular mechanism that may contribute to the difference in neural target gene sensitivity to these androgens; (b) up‐regulation of AR occurs only in the presence of agonists; © the mechanism of action of FLU in the brain involves inhibition of AR protein up‐regulation normally seen in response to androgen; and (d) FLU promotes AR nuclear translocation but not augmentation of cellular AR populations. These findings demonstrate that in vivo AR regulation in the brain basically parallels mechanisms proposed from results obtained with transfected cells and cell lines. © 1999 John Wiley & Sons, Inc. J Neurobiol 41: 505–512, 1999
It is very possible that our AR are out regulated, the plausible fix of the problem could be somebody who understand it and regulated it correctly.