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NAD (P)H‐quinone oxidoreductase 1 silencing aggravates hormone‐induced prostatic hyperplasia in mice
Author(s) -
Kim H.T.,
Kim Y.J.,
Park S.R.,
Ryu S.Y.,
Jung J.Y.
Publication year - 2018
Publication title -
andrologia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.633
H-Index - 59
eISSN - 1439-0272
pISSN - 0303-4569
DOI - 10.1111/and.12906
Subject(s) - dihydrotestosterone , testosterone propionate , hyperplasia , lncap , testosterone (patch) , endocrinology , medicine , finasteride , androgen receptor , chemistry , prostate , androgen , biology , hormone , prostate cancer , cancer
Summary NAD (P)H‐quinone oxidoreductase 1 ( NQO 1) is a highly inducible flavoprotein known to involve in various cellular defence mechanisms. In this study, we explored whether NQO 1 deletion affects hormone‐induced prostatic hyperplasia. Testosterone propionate (3 mg/kg, IP ) was injected into wild‐type ( WT ) and NOQ 1 knockout C57 BL /6 mice ( NQO 1 −/− ) for 14 consecutive days, and the samples were collected for biological and histochemical studies. The testosterone‐treated NQO 1 −/− showed about 140% higher prostate weight than the testosterone‐treated WT , with enhanced connective tissue and hyperplastic glands formations. However, increased dihydrotestosterone level after testosterone treatment was not significantly different between the WT and NQO 1 −/− . In contrast, the enhanced nuclear expression of proliferating cell nuclear antigen in NQO 1 −/− prostate confirmed aggravated prostatic hyperplasia in NQO 1 −/− . Moreover, the expression of heat shock protein ( HSP ) 90‐α was markedly increased in the NQO 1 −/− , and this was supported by increased testosterone‐induced nuclear androgen receptor expression in NQO 1‐silenced LNC aP cells. Testosterone‐induced prostate‐specific antigen expression was not reversed in NOQ 1‐silenced cells after finasteride treatment. Although the exact role of NQO 1 in prostatic hyperplasia remains unclear, the hyperplasia exacerbation due to NQO 1 deletion might be independent of type 2 5α‐reductase and might be related to enhanced androgen receptor affinity due to enhanced HSP 90‐α expression.