Androgenic Regulation of Oxidative Stress in the Rat Prostate

Abstract

Little is known about the roles of androgens in the regulation of redox state in the prostate, a cellular process believed to profoundly influence normal and aberrant prostate functions. We demonstrate that castration induced discrete oxidative stress (OS) in the acinar epithelium of rat ventral prostate (VP), as evident from marked increases in 8-hydroxy-2'-deoxy-guanosine and 4-hydroxynonenal protein adducts in the regressing epithelium. Testosterone replacement partially reduced OS in VP epithelia of castrates, but the level remained higher than in intact rats. Quantification of steady-state mRNA levels of 14 genes involved in the anabolism and catabolism of reactive oxygen species (ROS) showed that castration resulted in dramatic increases of three ROS-generating NAD(P)H oxidases (Noxs) including Nox1, gp91(phox), and Nox4, significant reductions of key ROS-detoxifying enzymes (superoxide dismutase 2, glutathione peroxidase 1, thioredoxin, and peroxiredoxin 5), and unchanged levels of catalase, glutathione reductase, gamma-glutamyl transpeptidase, and glutathione synthetase. Testosterone replacement in castrated rats partially reduced expression of Noxs but restored expression of superoxide dismutase 2, glutathione peroxidase 1, thioredoxin, and peroxiredoxin 5 to complete normalcy and induced a compensatory increase in expression of catalase, glutathione reductase, gamma-glutamyl transpeptidase, and glutathione synthetase in the regenerating VP. Expression of superoxide dismutase 1, glutathione S-transferase-pi, and glucose-6-phosphate dehydrogenase was unaffected by castration and testosterone replacement. These findings indicate androgen-deprivation induces OS in the rat VP through elevation of ROS anabolism and diminution of antioxidant detoxification. Androgen replacement partially reduces OS in rat VP to precastration levels. Expression of Noxs remained high amid a broad-based recovery of antioxidant defense mechanism(s). These data might have implications on the use of androgen blockade for prostate cancer prevention and androgen therapy for andropause treatment in elderly men.

Evaluation of estrogenic and androgenic activity of butylated hydroxyanisole in immature female and castrated rats

“…BHA also inhibited 2-aminofluorene induced DNA adduct formation in prostate cancer cell (Yeh et al, 2000). Oxidative stress was induced by castration but it was reduced by androgen replacement in acinar epithelium of rat ventral prostate (Tam et al, 2003). The additive effect of BHA on testosteronestimulated VP weight observed at present study may be related to the complementary action of BHA as an antioxidant, which increases the antioxidant activity of testosterone in castrated rats because the additive effect weak and only relative weight was increased.…”

Alteration of glyoxalases gene expression in response to testosterone in LNCaP and PC3 human prostate cancer cells

“…The upregulation of GI and GII by T may be the result of the presence in LNCaP cells of possible GI-and GII-mediated intracellular response mechanisms to androgen-induced oxidative stress. 31,32 As well known, oxidative stress leads to lipid peroxidation, which is an important pathway leading to the production of the intracellular toxic metabolite MG. 2 In addition, it has been described that androgens control lipid metabolism in human prostate cancer cells by inducing a marked accumulation of cytoplasmic lipid droplets, 33 likely giving a consequent enhanced lipid metabolism. Since MG also derives from this latter metabolic pathway, 2 enhanced androgen-stimulated lipid metabolism, likely leads to an overproduction of this cytotoxic metabolite.…”

The Protective Effect of Testosterone on Streptozotocin-Induced Apoptosis in β Cells Is Sex Specific

“…19,20 In tissues as the prostate, testosterone participates in defensive mechanisms of oxidative stress in rats, increasing the levels of antioxidant enzymes. 21,22 Because a sexual dimorphism caused by sex steroid hormones in the damage of pancreatic A cells has been demonstrated in animal models of diabetes mellitus, 6,7,23Y25 the present study was designed to evaluate if other steroids, in addition to testosterone, can protect pancreatic A cells against STZ-induced apoptosis in gonadectomized rats, to explore if antioxidant enzymes are involved in this cytoprotective effect, and to investigate if the protective effect of testosterone is sex specific.…”