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

作者：Kim H. -T.; Kim Y. -J.; Park S. -R.; Ryu S. -Y.^*; Jung J. -Y.^*

来源：Andrologia, 2018, 50(3): e12906.

DOI：10.1111/and.12906

• androgen receptor
• heat shock protein 90-
• NQO1
• prostatic hyperplasia
• type 2 5-reductase

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 (3mg/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- 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 5-reductase and might be related to enhanced androgen receptor affinity due to enhanced HSP90- expression.

• 出版日期2018-4