NAD(P)H‐quinone oxidoreductase 1 silencing aggravates hormone‐induced prostatic hyperplasia in mice

NAD(P)H‐quinone oxidoreductase 1 (NQO1) is a highly inducible flavoprotein known to involve in various cellular defence mechanisms. In this study, we explored whether NQO1 deletion affects hormone‐induced prostatic hyperplasia. Testosterone propionate (3 mg/kg, IP) was injected into wild‐type (WT) and NOQ1 knockout C57BL/6 mice (NQO1^?/?) for 14 consecutive days, and the samples were collected for biological and histochemical studies. The testosterone‐treated NQO1^?/? 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 NQO1^?/?. In contrast, the enhanced nuclear expression of proliferating cell nuclear antigen in NQO1^?/? prostate confirmed aggravated prostatic hyperplasia in NQO1^?/?. Moreover, the expression of heat shock protein (HSP) 90‐α was markedly increased in the NQO1^?/?, and this was supported by increased testosterone‐induced nuclear androgen receptor expression in NQO1‐silenced LNCaP cells. Testosterone‐induced prostate‐specific antigen expression was not reversed in NOQ1‐silenced cells after finasteride treatment. Although the exact role of NQO1 in prostatic hyperplasia remains unclear, the hyperplasia exacerbation due to NQO1 deletion might be independent of type 2 5α‐reductase and might be related to enhanced androgen receptor affinity due to enhanced HSP90‐α expression.