Sex hormone-induced alterations in the activities of antioxidant enzymes and lipid peroxidation status in the prostate of Noble rats.
BACKGROUND
Oxidative stress has been implicated in prostate carcinogenesis. In the Noble rat model, treatment of rats with testosterone (T) plus 17beta-estradiol (E(2)) induced dysplasia and adenocarcinoma. Previous reports from us and other have indicated a linkage between steroid hormones and oxidative status in prostate cells in vivo and in vitro. Here, we provide further evidence that androgens and estrogens could induce a lobe-specific shift of prooxidant-antioxidant balance and alterations in antioxidant enzyme activities, leading to oxidative stress in the rat prostate gland in vivo.


METHODS
Male Noble rats were subjected to single (T, E(2), or diethylstilbestrol [DES] alone) or combined (T + E(2) or T + DES) hormone treatments. Lipid peroxidation status and antioxidant enzyme activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione reductase (GR), glucose-6-phosphate dehydrogenase (G6PD) were assayed spectrophotometrically.


RESULTS
Treatment of rats with T did not alter lipid peroxidation in either the ventral prostate (VP) or the dorsolateral prostate (DLP). In contrast, exposure of rats to DES or E(2) modestly elevated lipid peroxidation in rat VP or DLP, respectively. Of importance, T + DES and T + E(2) treatments of rats induced marked increases in lipid peroxidation in the VP and the DLP, respectively. Antioxidant enzyme activities in the VP and DLP exhibited differential responses to sex hormone challenges. The activities of catalase, GPx, GR, and G6PD were mostly suppressed in either single or dual hormone-treated DLP, whereas there is a general increase of GR and G6PD activities in the VP after hormonal exposures. The changes in T + DES-treated VP were most dramatic with a marked activation of GPx (by one-fold), GR (by one-fold), and G6PD (by five-fold).


CONCLUSIONS
The lobe-specific differential responses of hormone-induced oxidative stress and modulations of antioxidant enzymatic defenses in the rat prostate suggest that reactive oxygen species may play a role in hormone-induced prostate carcinogenesis.
Tam
Neville N C
NN
Division of Urology, Department of Surgery, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
Ghatak
Shibnath
S
Ho
Shuk-Mei
SM
D000818:Animals; D002374:Catalase / Q000378:metabolism; D004054:Diethylstilbestrol / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D018384:Oxidative Stress; D011467:Prostate / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013739:Testosterone / Q000494:pharmacology*
D004968:Estrogens, Non-Steroidal; D017382:Reactive Oxygen Species; D013739:Testosterone; D004958:Estradiol; D008315:Malondialdehyde; D004054:Diethylstilbestrol; D005954:Glucosephosphate Dehydrogenase; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase