PubMed · 9146650
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
S L Goldenberg, M E Gleave, N Bruchovsky, P Rennie. 1997. Re: Editorial comment.. https://doi.org/10.1016/s0022-5347(01)64759-1
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
BACKGROUND: The meta-analysis of maximal androgen blockade (MAB) concluded that there is no survival advantage of MAB over castration alone. However, the results from the largest trials yield conflicting results. METHODS: The design and results of three trials were examined. RESULTS: Most studies were planned to detect an over-optimistic difference in survival and immature data were published. The survival curves show that statistical assumptions are not fulfilled. Excluding from the meta-analysis all trials where a negative impact of disease flare on survival could not be excluded resulted in no difference in survival between MAB and castration. CONCLUSIONS: Trials of MAB should be planned to detect differences of no more than 5-10% in median survival. The analyses should only be carried out on mature data and should take into account the possibility of a negative impact on survival due to disease flare if no anti-androgen has been given initially with an LH-RH agonist.
Over the past 20 years, the documented increase in the disorders of male sexual differentiation, such as hypospadias, cryptorchidism, and micropenis, has led to the suspicion that environmental chemicals are detrimental to normal male genital development in utero. Male sexual differentiation is critically dependent on the normal action of androgens, and unbalanced androgen/estrogen ratios can disturb it. Environmental xenoestrogens (such as herbicides, pesticides, PCBs, plasticizers, and polystyrenes) that mimic estrogens or environmental antiandrogens (such as polyaromatic hydrocarbons, linuron, vinclozolin, and pp'DDE) that disturb endocrine balance, cause demasculinizing effects in the male foetus. These environmental chemicals are often referred to as endocrine disruptors: they are thought to mimic endogenous estrogens by entering the cell, binding to the receptor and activating transcription, they may also antagonize normal androgen action. We have established numerous cell lines to assess the estrogenicity and antiandrogenicity of compounds found in the environment and to identify new products present in wastewater effluents that are able to disrupt endocrine functions. Several cell lines responding to estrogens have been obtained in our group, including cells with different enzymatic equipment and cells expressing chimeric receptor or natural estrogen receptors alpha and beta. These cell lines have proved to be useful for assessing the biological activity of pesticides, fungicides, and chemicals found in plastic or discarded in the environment. In order to generate a powerful tool for the investigation of androgen action and the rapid screening of potential antagonists, we developed a new stable prostatic cell line. The PALM cell line is an original cellular model to characterize the response of hAR, and it provides an easy and rapid bioluminescent test to identify new antagonists. We also developed a model based on a fusion protein between the androgen receptor (AR) and the green fluorescent protein (GFP) to study the intracellular dynamics of AR. The GFP-AR model was applied to define the ability of several xenoestrogens and antiandrogens to inhibit the nuclear transfer of AR. The ubiquitous presence of endocrine disruptors in the environment and the increased incidence of neonatal genital malformation support the hypothesis that disturbed male sexual differentiation may in some cases be caused by increased exposure to environmental xenoestrogens and/or antiandrogens.
During the last decade, the possible effects of xenobiotics on male reproductive health have resulted in great concern. More recently, evidence of antiandrogen effect in vivo by certain chemicals has been reported. The classical Hershberger in vivo assay determining organ weight changes can be improved by measuring hormone levels as well as determining changes in gene expression of androgen-responsive genes. A real-time RT-PCR method using LightCycler technology (Roche) suitable for quantitative determination of gene expression is described. The technique combines rapid thermocycling with online fluorescence detection of PCR product formation. In this study, investigation of expression of prostate specific binding protein polypeptide C3 (PBP C3) and testosterone-repressed prostatic message 2 (TRPM-2) in the ventral prostate was performed in 60-days-old castrated Wistar rats treated daily with testosterone with or without addition of flutamide or vinclozolin for 7 days in total. We show that we can quantify the level of gene expression by use of LightCycler technology, supported by changes in reproductive organ weights as well as in hormone levels, and that analysis of gene expression levels is an even more sensitive endpoint.