soulsurvivor316
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Abstract
Recent studies have demonstrated that retinoic acid (RA) can repress the growth of human prostatic epithelial cells. Since the proliferation of prostate cells is highly dependent on androgen stimulation, presumably via its cognate receptor, we investigated the effects of RA on the expression of the androgen receptor and other androgen-regulated genes in the human prostatic adenocarcinoma cell line LNCaP. Using a radioligand binding assay, we found that androgen-binding activity was reduced 30-40% in cells treated with 10-5 M RA plus 6 nM dihydrotestosterone (DHT), as compared to cells with the androgen alone. Moreover, the reduction of the androgen receptor (AR) was not accompanied by alteration of the ligand-binding affinity. Concomitant changes in the function of AR were manifested by a dramatic reduction in AR-mediated transcription activity in a transfection experiment. Androgen-induced levels of both prostate-specific antigen (PSA) and human glandular kallikrein-1 (hKLK2) mRNAs were significantly repressed by RA in a dose- and time-dependent manner. Consistent with this finding, androgen induction of PSA glyco-protein was also repressed by RA, with maximal inhibition occuring at 10-5 M. These data suggest that the suppression of proliferation and function of prostatic cells by RA may be via modulatory effects on the AR.
It seems that if Retin-A is used for a long time, it may reduce the number of androgens by 30-40%. That appears to be a very significant number and I want to get other's thoughts on this.
Also, if this is true, wouldn't a combo of retin-a, topical spironolactone and nizoral be a potent anti-androgenic regimen? If I had to take a guess, I would say that androgen receptor activity should be reduced by more 60% on such a regimen.
Recent studies have demonstrated that retinoic acid (RA) can repress the growth of human prostatic epithelial cells. Since the proliferation of prostate cells is highly dependent on androgen stimulation, presumably via its cognate receptor, we investigated the effects of RA on the expression of the androgen receptor and other androgen-regulated genes in the human prostatic adenocarcinoma cell line LNCaP. Using a radioligand binding assay, we found that androgen-binding activity was reduced 30-40% in cells treated with 10-5 M RA plus 6 nM dihydrotestosterone (DHT), as compared to cells with the androgen alone. Moreover, the reduction of the androgen receptor (AR) was not accompanied by alteration of the ligand-binding affinity. Concomitant changes in the function of AR were manifested by a dramatic reduction in AR-mediated transcription activity in a transfection experiment. Androgen-induced levels of both prostate-specific antigen (PSA) and human glandular kallikrein-1 (hKLK2) mRNAs were significantly repressed by RA in a dose- and time-dependent manner. Consistent with this finding, androgen induction of PSA glyco-protein was also repressed by RA, with maximal inhibition occuring at 10-5 M. These data suggest that the suppression of proliferation and function of prostatic cells by RA may be via modulatory effects on the AR.
It seems that if Retin-A is used for a long time, it may reduce the number of androgens by 30-40%. That appears to be a very significant number and I want to get other's thoughts on this.
Also, if this is true, wouldn't a combo of retin-a, topical spironolactone and nizoral be a potent anti-androgenic regimen? If I had to take a guess, I would say that androgen receptor activity should be reduced by more 60% on such a regimen.
