Friday, June 28, 2013

Prostate cancer

One of the most relevant pieces of evidence in favor of the causal association between sex steroids and prostate cancer has been provided by animal studies. Long-term administration of testosterone and estradiol to Noble rats results in a high incidence of adenocarcinomas in the dorsolateral prostate. The combined treatment of intact Noble rats with testosterone and estradiol, but not the separate administration of these gonadal steroids alone, induced florid dysplasia and markedly elevated mitotic index in the rat dorsolateral prostates. It has been suggested that protracted androgen-supported estrogen-enhanced stimulation of cell proliferation may be required to develop dysplastic lesions in the rat prostate. More recently, a 5-8-week treatment with testosterone and estradiol induced atypical hyperplasia and carcinoma in male nude mouse grafted with retinoblastoma-null mouse embryonic prostates, suggesting that deletion of the retinoblastoma gene predisposes prostatic epithelium to hyperplasia and enhances its susceptibility to hormonal carcinogenesis.

High levels of endogenous gonadal steroids are considered to be risk factors for prostate cancer. However, while the association of sex steroids with prostate cancer is supported by biological evidence, epidemiological studies have reported inconclusive data. Analytical studies using direct measurement of serum steroid levels in relation to prostate cancer risk have shown inconsistent results. Measurement of endogenous hormones in blood or urine poses many methodological and logistic problems, including variations in biological specimen collection and assay methods. These problems may explain, at least in part, the inconsistency of previous study results.

In specific tissues of the body, including prostate, the balance between androgens and estrogens may differ significantly from that in the plasma, being dependent upon the presence and activity of steroid-metabolizing enzymes, such as 5a-reductase and aromatase.

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