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The past decade has witnessed significant advances in our understanding of the biology of prostate cancer. Androgen ablation/androgen receptor inhibition remains as the mainstay of treatment for advanced prostate cancer. Our understanding of the biology of prostate cancer has increased exponentially owing to advances in molecular biology. With this knowledge many intriguing issues have come to light, which clinicians and scientists alike strive to answer. These include why prostate cancer is so common, what drives the development of prostate cancer at a molecular level, why prostate cancer appears refractory to many families of cytotoxic chemotherapeutics, and why prostate cancer preferentially metastasizes to bone. Two clinical forms of prostate cancer have been identified: indolent organ confined disease, which elderly men often die of, and aggressive metastatic disease. A method of distinguishing between these two forms of the disease at an organ-confined stage remains elusive. Understanding the mechanisms of castrate resistance is a further issue of clinical importance. New trials of treatments, including molecular agents that target prostate cancer from a range of angles, have been instituted over the past 10-15 years. We can look at these trials not only as a chance to investigate the effectiveness of new treatments but also as an opportunity to further understand the complex biology of this disease.

The presence of unidentified estrogens and androgens in effluents from pulp and paper mills is well documented. However, their role in effluent effects on fish reproduction remains unclear. The objective of this study was to investigate the hypothesis that reproductive impacts of a modern pulp mill effluent are mediated by androgens and/or estrogens in the effluent. Male and female threespine stickleback were exposed to biologically treated Canadian bleached kraft mill effluent under flow-through conditions in the laboratory at 0, 1, 10 and 100% (v/v) dilutions. After 7 and 21 d of exposure, steroidogenesis was assessed using in vitro incubations of gonadal tissue in both males and females. mRNA expression of the estrogen-regulated gene vitellogenin, and the androgen-responsive gene spiggin were assessed using quantitative RT-PCR in the livers of male and posterior kidneys of female stickleback, respectively. Hepatic 7-ethoxyresorufin-O-deethylase (EROD) activity was assessed in both sexes. Effluent extracts were examined for estrogenic and androgenic bioactivity using receptor binding bioassays, and were screened for pulp and paper related extractives and steroidal androgens using GC-MS. This effluent up-regulated spiggin mRNA in the kidney of female stickleback at 10% and 100% (v/v) effluent at 21 d, but not at 7 d of exposure. This change at the mRNA expression of the gene was associated with an increase in cell height in kidney proximal tubule epithelial cells at 100% effluent after both 7 and 21 d. Liver vitellogenin mRNA in male stickleback was not induced at either 7 or 21 d. EROD was induced at 10 and 100% after 21 d of exposure in both sexes, but not after 7 d of exposure. Despite evidence of exposure to androgens, there was no reduction in steroidogenic capacity at any effluent dilution. Effluent extracts were capable of eliciting the displacement of androgens and estrogens from receptors, but androgenic potency was 4-fold greater. A screen of more than 30 androgenic androstane steroids showed no detections. Hence, the androgenic constituents in this particular effluent remain unknown.

Background—There is currently no effective treatment for recurrent hormone refractory carcinomas of the prostate gland. An understanding of the underlying mechanisms responsible for the progression of these lesions is likely to be important for the development of new therapeutic approaches. Recently, it has been suggested that the transition to a hormone independent state is accompanied by increased proliferation and bcl-2 gene expression, as well as by a decreased apoptotic state. Aim—To investigate the possible role of Bcl-2 and other cell cycle regulating proteins in the development of prostatic tumours. Methods—Immunohistochemistry was used to study the relation between the expression of Bcl-2 and the androgen receptor, as well as p21WAF1/CIP1 (p21), and cyclin D1 status, in a series of 89 prostate cancer samples taken before androgen withdrawal treatment. Results—Androgen receptor negative tumours expressed significantly higher amounts of Bcl-2 than those prostate carcinomas with low/medium androgen receptor values. However, in tumours expressing the highest amounts of androgen receptor, Bcl-2 expression was also high. A significant positive relation between Bcl-2 and p21 expression, as well as an inverse relation between Bcl-2 and cyclin D1 expression, was noted. Androgen receptor positive samples also expressed significantly higher amounts of cyclin D1. Conclusions—These results suggest that p21 and cyclin D1 expression in prostatic cancer might be modulated by Bcl-2 and by androgens and in turn this could be relevant to the progression of prostatic cancer.

1. After the administration of large doses of androsterone, epiandrosterone, dehydroepiandrosterone and testosterone to mice, females excreted more of the dose conjugated with sulphuric acid than did males. 2. Liver slices from female mice conjugated androgens with sulphuric acid to a greater extent than did slices from males. 3. Sulphotransferase preparations from livers of female rats and mice catalysed the formation of dehydroepiandrosterone sulphate at a faster rate than preparations from livers of the male animals. 4. A possible explanation for the observed sex differences is discussed.