Remains in the R Potential inhibitors of Ar 5 in the management of prostatic intraepithelial neoplasia and Pr Prevention of prostate cancer.5 This report reviews current knowledge on the R The androgens and LY317615 Enzastaurin the AR system 5 in prostate disease and emphasizes their importance in reducing the risk of prostate cancer. Androgens play an R Essential for the development of prostate and function, but are also involved in prostate disease pathogenesis.6 without androgens, prostate cancer has not developed and the gland would atrophy if androgen support withdrawn.5 The most important and androgen DHT from testosterone was functionally active by types 1 and 5 produced AR 2.6,7 This leads to a concentration of 5-h time ago DHT testosterone in prostate cells c, v, a concentration 11 times h her testosterone, free testosterone blood.
4 diffuse directly into the epithelial cells or stromal cells the prostate, where it is rapidly and irreversibly converted to DHT by the 5 AR positioned at the nuclear membrane. DHT binds to the androgen receptor with high affinity t, and this complex, mediated by the coregulators as NCOA3 is transported into the nucleus. Once inside, this newly formed complex binds to androgen, initiates transcription and ultimately controlled On the regulation of cell cycle, cell growth and AR differentiation.7 5, has r The biological importance to be able to focus intraprostatic DHT, when / if the serum testosterone levels are physiologically low. Hen as increased serum testosterone levels, There is less need to help these 5 AR, androgens accumulate in prostate.
8 In a study by Wright and his colleagues 8 Sprague-Dawley rats were castrated for 2 weeks erm Their prostate resembled completely be reduced complete, and then were implants of testosterone, with different dimensions in the presence or absence of an inhibitor of 5 AR. Dramatic increase in prostate weight were seen, even at the lowest serum testosterone levels in the absence of inhibition of AR 5, w While clearly h Here serum testosterone were necessary to achieve a growth of the prostate in the presence of 5 AR inhibition.8 The difference in the activity tons of testosterone v. To support the growth of the prostate is small compared with DHT in the ratio ratio of intraprostatic androgen concentrations, but it is much larger it, if the serum testosterone levels Considered .
8 A key question in relation to the effect of androgens is whether testosterone and DHT are responsible for the regulation of expression of various genes in response to androgens in the prostate. Experimental studies show that testosterone is st Stronger than DHT in stimulating the expression of numerous genes in response to androgens decreased the expression of these genes prostate.9 androgenresponse is probably associated with a differentiation of androgen dependence in specific connection Dependence and prostate Including, Lich the maintenance of very important F of prostate cells ability to undergo apoptosis, and less with stimulation of the proliferation of the prostate w during growth.9 other hand, high levels of DHT result associated intracellular r in cell proliferation and cell differentiation in delay, an important fact considering the treatment of prostate disease early or Pr kanzerosen with 5-AR inhibition. 5 AR2 has always been considered clinically
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