ENDO 2005 targets chemicals impact on environment, health

Latest research presented during Endocrine Disrupters Forum studies find variety of chemicals in the environment affect human reproduction...

SAN DIEGO, June 3, 2005 (PRNewswire) -- A day-long forum on endocrine disrupting chemicals as part of ENDO 2005 will be held today at the San Diego Convention Center, featuring the latest research on the connection between natural and synthetic compounds that mimic hormones or block hormones' effects. Recent research has found endocrine disrupting chemicals (EDCs) cause reproductive, metabolic and developmental disorders and cancers with their effects crossing generations.

ENDO 2005, June 6-7, is being held by the Endocrine Society to present latest research on these compounds and their effect on the environment and health.

Leading endocrine investigators will present the most current information and recent discoveries on how hormonally-active compounds in food, drinking water and the environment are increasingly linked to endocrine-related dysfunctions. New research will also highlight the dangers of fetal exposure to EDCs as a risk factor for adult onset of infertility, obesity and breast and prostate cancer.

Former Endocrinology editor-in-chief, Dr. Kenneth Korach, will give the keynote speech. Korach is currently the Program Director of the Environmental Disease & Medicine Program with a focus on hormone receptors and mechanisms. Korach chaired The Endocrine Society's forum on EDCs in 2001 and served as the co-organizer of the Keystone Symposium on Endocrine Disruptors.

In addition to the Forum, four new studies will be featured in a press conference at the San Diego Convention Center on Saturday, June 4, 2005 at 2:00 p.m. The studies include reports on the possible harmful effects of uranium in drinking water and soy infant formula and the effect of herbicides on human fertility and reproduction, as well as the effects of pesticides on the human prostate.

Water in Navajo Nation Could Cause Reproductive Problems
A study by Dr. Stefanie Whish, Northern Arizona University, uncovered potential reproductive implications for the Navajo Nation. After decades of uranium mining and milling, there are hundreds of un-reclaimed mines and mine tailings on the Navajo Nation. The U.S. EPA has analyzed 30 of 110 Chapters on the Navajo Reservation and identified scores of drinking water sources with uranium that exceed the safe drinking water level.

Recent studies show many heavy metals have estrogenic properties in vivo and in vitro; however, uranium has not been tested. Dr. Whish's hypothesis was that uranium mimics estrogen activity eliciting estrogen sensitive responses in vivo. She tested if the changes were dependent on the estrogen receptor. Her method was to treat immature ovariectomized mice with uranyl nitrate (UN) or diethylstilbestrol (DES) in drinking water for 10 days and while treating with sesame oil vehicle or ICI 182,780, an estrogen receptor antagonist.

Statistically significant increases in uterine weight, accelerated vaginal opening and persistence of vaginal cornified cells were observed in UN (30 ug/L) and DES (50 ug/L) treated mice compared to mice drinking control water and ICI 182,780-treated mice, indicating that uranium elicited responses were dependent on the estrogen receptor. Results were observed at UN concentrations U.S. EPA safe drinking water concentration, which are exceeded in many drinking water sources on the Navajo Nation.

The results suggest that uranium is estrogenic and may be an endocrine disruptor that can cause reproductive problems in the Navajo people.

Infant Formula Ingredient May Disrupt Female Reproductive Development
Previous studies have shown that developmental exposure to the soy phytoestrogen Genistein, which can be found in soy-based infant formulas (which have been banned in the United Kindgom), causes altered ovarian differentiation. Dr. Retha Newbold of the National Institute of Environmental Health Sciences will present a study on her research on whether Genistein's potential to disrupt ovarian differentiation could thereby alter reproductive function in mice and by extension, humans.

The results demonstrated marked altered reproductive function in mice taking Genistein including altered vaginal opening, abnormal estrus cycles, early reproductive senescence and subfertility/infertility at doses of Genistein that are at human infant exposure levels.

Common Herbicide Causing Major Developmental Disruption
Atrazine, the most widely used herbicide in the world, is potentially contributing to the recent global amphibian decline, since it demasculinizes frogs possibly by aromatase stimulation. In a study by Dr. WuQiang Fan, Graduate School of Medical Science, Kyushu University, Japan, there are suggestions that herbicides like atrazine might stimulate human aromatase via promoter II in an Ad4BP/SF1 dependent manner, which may have significant implications for the environment and public health.

Atrazine has been shown to induce aromatase in H295R human adrenocortical carcinoma cells. Dr. Fan and colleagues recently reported that transactivation of Ad4BP/SF1 on human aromatase promoter II (ArPII) can be further enhanced by protein kinase A (PKA) signal pathway. By applying this system, 55 environmental endocrine disruptors were screened for interference with the Ad4BP/SF1-mediated ArPII activation. Chloro-s-Triazine herbicides (atrazine and simazine) were found to stimulate the Ad4BP/SF1-mediated ArPII activity by a factor of 2 to 3, whereas neither chemical stimulated ArPII in the absence of Ad4BP/SF1, suggesting the stimulatory effect is Ad4BP/SF1 dependent.

The aromatase enzymatic activity was found unchanged by the herbicides in the ovarian granulose-like tumor cell line (KGN), which does endogenously express Ad4BP/SF1, albeit at a low level. However, when the cells were infected with Adeno-Ad4BP/SF1 but not Adeno-LacZ virus, the stimulatory effect was completely restored. In addition, real time RT-PCR revealed that aromatase mRNA levels in KGN cells were also elevated by either atrazine or simazine only in the presence of Adeno-Ad4BP/SF1. The herbicides changed neither protein levels nor promoter activity of Ad4BP/SF1. Intriguingly, the interaction of Ad4BP/SF1 with its repressor DAX1 was found weakened by both chemicals, especially atrazine.

Effects of Pesticides on Human Prostate
Since the late 1990s, concern has been growing about substances that could be hormone active, the so-called endocrine disrupters (ED). As part of the European Union supported interdisciplinary project COMPRENDO (EVK 1-CT-2002- 00129), Dr. Susan Lo and colleagues attempted to detect and compare the antiandrogenic/androgenic effects of 10 different pesticides and, for comparison, five pharmaceuticals with various test systems.

The task of this study was to test the chemicals regarding their effect on human prostate cells. Research found the organotin compounds TBT and TPT to be the strongest inhibitors. Comparing the two enzyme assays in terms of screening putative ED, the tissue assay is the more sensitive method, but as the cell assay provides regulatory systems to compensate the disturbance of the steroid hormone metabolism, it represents the more realistic situation.

Founded in 1916, The Endocrine Society (www.endo-society.org) is the world's oldest, largest, and most active organization devoted to research on hormones, and the clinical practice of endocrinology. Today, the Society's membership consists of over 12,000 scientists, physicians, educators, nurses and students in more than 80 countries. Together, these members represent all basic, applied, and clinical interests in endocrinology. The Endocrine Society is based in Chevy Chase, Maryland.

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