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In this feline hair loss near tail cells were exposed to 25 microM finasteride, at which concentration 50% of both PSA mRNA and protein were inhibited. Our previous study sho that PSA was not only present

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in conditioned medium of the PSA-positive

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LNCaP cells but was also detectable in small amounts in PSA-negative cell lines, PC-3 and DU-145 (L. Down-regulation

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antigen expression by finasteride through inhibition of complex formation between androgen receptor and steroid receptor-binding consensus in the promoter of the PSA fletch in LNCaP cells.As a specific competitive inhibitor of alpha-reductase,

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is being extensively used for the treatment of benign prostatic hyperplasia and in experimental settings for prostate cancer. The promoter of the PSA horatio contains several well-known cis-regulatory elements. This effect of finasteride to block cholesterol side-chain cleavage may be species-specific. A strong correlation between binding of nuclear factors to SRBC and the level of PSA present in the conditioned medium and cell extracts was found in these three cell lines, whereas no such correlation with binding was obtained using Sp1 oligonucleotide as a probe. Our data indicate that inhibition of complex formation between SRBC and nuclear proteins due to the remarkable decrease in the level of androgen receptor plays a key role in the down-regulation of PSA tracy expression by finasteride in LNCaP cells. Among them, steroid receptor-binding consensus (SRBC) has been identified as a functional androgen-responsive element. Inhibition is dose-dependent with half maximal inhibition occurring at 10 ng/ml, a concentration significantly less than serum concentrations detected in finasteride-treated patients. Experiments to localize the site of inhibition by this compound revealed that the 3 beta-hydroxysteroid dehydrogenase delta 5-->delta

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4 isomerase enzyme was not blocked by finasteride, but that cholesterol side-chain cleavage was inhibited. Inhibition is readily detected in the mouse-derived

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MA-10 cells; however, human granulosa cell steroidogenesis is finasteride-insensitive while rat Leydig cell steroidogenesis is only minimally effected by finasteride.. As a major component of DNA-protein

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complexes, the level of androgen receptor was dramatically decreased in the cells treated with finasteride. Thus, both dibutyryl-cAMP-stimulated and 22-hydroxycholesterol-stimulated steroidogenesis were inhibited by finasteride. Finasteride blocks progesterone synthesis in MA-10 Leydig tumor cells.The 5 alpha-reductase inhibitor, finasteride, inhibits progesterone synthesis in the MA-10 Leydig tumor cells.

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