| Research Briefs :: Archives 2000-2010 |
| Archived Briefs 2010 Excreted BPA correlated with hormone levels in men
web link...
|
|
Archived Briefs 2009
This month a paper in Environmental Health Perspectives reports on its careful examination of data from the NHANES study—a large longitudinal examination of health data across the US population. Pulling data on the concentrations of BPA in the urine of fasting individuals, the researchers looked to examine the half-life of BPA in humans. They found a definite decrease in fasting for 4 to 9 hours, but longer fasting showed no significant decline in BPA excretion. The scientists involved identify two possible explanations—a significant amount of BPA is stored in body fat, or there are other non-food exposures to BPA. BPA is used in many plastics used in prepared and preparing food, including the lining of cans, and is often found in disposable eating utensils. Recent studies show as well that it can move from PVC pipes to water, and that single-serving disposable plastic drink containers may leach BPA as well. Certainly more research needs to follow these results, but for now concern about BPA continues to grow...
Nuclear Receptors are relatively ancient, being found in all metazoans, and thus reaching back to the origin of multicellular organisms. Thus it should come as no surprise that mulitcellular organisms should show the evolution of parallel systems to coordinate extrinsic and intrinsic signaling using different Nuclear Receptors. An organism in which Nuclear Receptors are best studied is the model nematode Caenorhabditis elegans. A recent review of Nuclear Receptor function in C elegans suggests that they have developed their own functional version of an endocrine system which uses ligand-gated proteins analogous to, but different from, those in the chordate endocrine system. Comparing the functions of these two systems should be a very productive path to further understanding the function and dysfunction of these transcription factors their control networks, and their downstream effects...
A recent review examines sex determination in amphibians, and suggests why sex reversal is possible in these animals. The diversity of genetic sex determination in modern amphibians suggests that chromosomal sex determination has occurred multiple times in this clade. In addition, the development of amphibian gonads is determined by levels of either CYP19 (for feminization) or CYP17 (for masculinization). Thus the sex of any individual, no matter their sex chromosome configuration, may be reversed. Since Fox and Sox genes, which are autosomally located, control CYP19 levels, exogenous effectors of these factors, or of CYP19 and CYP17 directly, may influence sex...
Another study, from the same lab, now reports that the estrogen receptor of annelid worms binds not only estrogen, but is either activated or antagonized by several known endocrine receptors. Thus, estrogen appears to have bound to an estrogen receptor since the origin of bilaterians about 600 million years ago...
The estrogen receptor is a relatively well-studied example of an epigenetically controlled gene. Since the estrogen receptor is so important developmentally, behaviorally, and in susceptibility and recovery from disease, its epigenetic control is very important to understand. This review summarizes evidence of maternal behavior affecting estrogen receptor epigenetics, suggesting that maternal behavior may be non-genetically inherited...
A research article just published reports on experiments exposing cancer cells to common anticancer drugs in the presence of BPA at low nanomolar concentrations. The authors report that BPA conferred protection to both estrogen receptor a positive and negative cell cultures...
|
|
Archived Briefs 2008
A recent study on the biology of steroid synthesis and gene sequences support this hypothesis. Bryan et al. (Sex Steroids and their receptors in lampreys) examined both steroid presence and function, and receptors for steroids, in lampreys. Lampreys are members of the oldest group of vertebrates (gnathostomes, or jawless craniates, in phylogenetic terms). Lampreys have and use estrogen (in the form 17b estradiol) as a hormone in both males and females. Their primary androgen is androstenedione (a precursor in biosynthesis to testosterone)--they seem to have a nuclear receptor for it. They also use 15a hydroxyprogesterone. This seems to indicate that it is possible that the first steroid-hormone and receptor pair was estrogen, and that through evolution the some of the precursors in the synthetic pathway were adopted into use as hormones over time. Another pair of studies (Adaptive evolution of mammalian aromatases by Conley et al. and The human progesterone receptor shows evidence of adaptive evolution by Chen et al.) provide evidence of adaptive evolution in steroid synthesis and steroid receptor function. Many comparative studies of steroid biology have been descriptive searches attempting to identify hormones or receptors in different species. These two papers suggest that a phylogenetic approach might be more fruitful, and that such studies might help us understand functional mechanisms of hormonal signaling by extending our lab experiments with ones constructed by nature... web link #1...
|
|
Archived Briefs 2007
|
|
Archived Briefs 2006 In the journal Endocrinology is a report form Retha Newbold's lab, on the results of experiments with mice exposed neonatally to the phytoestrogen genistein. In a dose-dependent manner the mice developed abnormalities in breast development. They also exhibited elevated levels of progesterone receptor and estrogen receptor beta, while estrogen receptor alpha levels were decreased. It is possible that these modified receptor levels are responsible for the morphological changes. These results add to the growing literature on the fetal basis of adult diseases, and suggest that in developmentally related diseases, exposure to exogenous chemicals at critical periods can be identified as causes.
These ethnic and BMI factors may make it difficult to identify the effects of exogenous chemicals on age at puberty.
Menstrual and reproductive characteristics of women whose mothers were exposed in utero to diethylstilbestrol (DES) A new article in the International Journal of Epidemiology shows for the first time transgenerational effects of DES in humans. Prenatal exposure of human females to diethylstilbestrol (DES) is associated with adult reproductive dysfunction. Experiments with mice, which show homologous DES outcomes, have suggested that DES exposure causes epigenetic changes transmissable to daughers of those prenatally exposed. This study examines the daughters of women exposed to DES and finds an increase in reproductive disorders, including a higher age at menarche, and higher incidence of irregular menstrual periods.
Endocrine-Related Resources from the National Institutes of Health Resources currently available to the scientific community that may be of interest for endocrinology research are described briefly here. More information is available through The Endocrine Society Home Page (http://www.endo-society.org). web link... Paracrine signaling through the epithelial estrogen receptor α is required for proliferation and morphogenesis in the mammary gland Estradiol is a major regulator of postnatal mammary gland development and thought to exert its effects through estrogen receptor α (ERα) expressed in the mammary gland stroma and epithelium. Previous studies, however, were confounded by the use of an ERα mutant strain that retains some of the protein with transactivation activity. Here, we use an ERα–/– mouse strain in which no ERα transcript can be detected to analyze mammary gland development in the complete absence of ERα signaling. The ERα–/– females show no development beyond a rudimentary ductal system. By grafting ERα–/– epithelium or stroma in combination with ERα WT stroma or epithelium, we show that the primary target for estradiol is the mammary epithelium, whereas a direct response of the mammary stroma is not required for mammary gland development to proceed normally. Mammary glands reconstituted with ERα–/– mammary epithelium exposed to pregnancy hormones show increased transcription of milk protein genes, indicating that ERα signaling is not an absolute requirement for a transcriptional response to pregnancy hormones. When ERα–/– mammary epithelial cells are in close vicinity to ERα WT cells, they proliferate and contribute to all aspects of mammary gland development, indicating that estradiol, like progesterone, orchestrates proliferation and morphogenesis by a paracrine mechanism, affecting nearby cells in the mammary epithelium... web link... Secondary sex ratios and male lifespan: Damaged or culled cohorts No one really knows what initiates puberty, that time in life when young change into sexually mature adults. But researchers have deciphered some of the chemical signals that control puberty's molecular starter switches in monkeys, according to results published in the February 8 issue of the Proceedings of the National Academy of Sciences. When the time is right, possibly based on size or internal clock, the KISS-1 gene activates production of the peptide hormone kisspeptin, the research team reports. Kisspeptin then teams with special receptors called GPR54 in the brain's hypothalamus to spark the region's release of puberty-inducing gonadotropin-releasing hormone (GnRH). GnRH, in turn, signals the pituitary gland to release gonadotropin hormones, such as luteinizing hormone, that trigger changes in the ovaries and testes beginning puberty. Previous studies found humans and mice with nonworking GPR54 receptors didn't enter puberty. In the new study, increased levels of GnRH in castrated male rhesus monkeys (Macaca mulatta) given kisspeptin and measured gene expression in the brains of male and female monkeys suggest the KISS-1 and GPR54 actions "contribute to the pubertal resurgence of pulsatile GnRH release, the central drive for puberty." web link... |
|
Archived Briefs 2005 Chemicals and genes team up to cause disease Exposure to environmental chemicals during early-life development can permanently alter or reprogram normal hormone responses causing cancer to develop in those with certain genetic makeups, research findings show. The gene-environment duo changes how reproductive tissue responds to estrogen by altering how hormonally-activated genes are expressed, leading to cancer and other diseases later in life, according to results published in the June 14 issue of the "Proceedings of the National Academy of Sciences". Almost twice as many rats exposed early in life to the environmental estrogen diethylstilbestrol (DES) and genetically predisposed to uterine cancer got tumors than unexposed animals with the gene defect, reports Cheryl L.Walker, professor at the M.D. Anderson Cancer Center, and colleagues. The findings may explain why some get cancer and others don¹t and confirms that genetics and environment can interact during development to change a gene¹s function and cause disease... http://www.pnas.org/cgi/content/abstract/102/24/8644
KISS kick starts puberty No one really knows what initiates puberty, that time in life when young change into sexually mature adults. But researchers have deciphered some of the chemical signals that control puberty's molecular starter switches in monkeys, according to results published in the February 8 issue of the Proceedings of the National Academy of Sciences. When the time is right, possibly based on size or internal clock, the KISS-1 gene activates production of the peptide hormone kisspeptin, the research team reports. Kisspeptin then teams with special receptors called GPR54 in the brain's hypothalamus to spark the region's release of puberty-inducing gonadotropin-releasing hormone (GnRH). GnRH, in turn, signals the pituitary gland to release gonadotropin hormones, such as luteinizing hormone, that trigger changes in the ovaries and testes beginning puberty. Previous studies found humans and mice with nonworking GPR54 receptors didn't enter puberty. In the new study, increased levels of GnRH in castrated male rhesus monkeys (Macaca mulatta) given kisspeptin and measured gene expression in the brains of male and female monkeys suggest the KISS-1 and GPR54 actions "contribute to the pubertal resurgence of pulsatile GnRH release, the central drive for puberty." http://www.pnas.org/cgi/content/abstract/102/6/2129 EDCs alter genetics; Impacts seen for four generations Environmental agents may have longer lasting effects than previously thought, according to new research from Washington State University. Two endocrine disrupting compounds, when given to pregnant rats during the critical period when sex organs form into male or female, permanently altered the chemical switches that control genetic processing, reports Michael Skinner and colleagues in the June 3 issue of the journal Science. The genetic changes resulted in lowered fertility and sperm health for four generations of the male progeny. The estrogenic methoxychlor and the antiandrogen vinclozolin changed the way certain genes were turned on and off - a genetic alteration known as epigenetics - rather than promoting mutations by changing DNA sequences, the authors' conclude. The study is the first to find that epigenetic changes induced by environmental toxins can persist for generations. The results could lead to a better understanding of disease, genetics, and evolution... http://www.sciencemag.org/cgi/content/full/308/5727/1466/DC1 http://www.sciencemag.org/cgi/content/summary/308/5727/1391a BPA in womb increases breast cancer risk at puberty Female mice born to mothers given low doses of bisphenol A (BPA) during pregnancy had aberrant mammary gland development at puberty, finds a study published online May 26 in the journal Endocrinology. The increased tissue growth, observed through higher number and area of ductal tissue branching at puberty and more ducts in the older offspring, are factors associated with increased breast cancer risk in humans, the international team of researchers report. The industrial chemical BPA mimics estrogen and is used in polycarbonate plastics, food can resins, and dental sealants. Because the widespread compound can leach from products, most people have measurable amounts in their bodies causing some to be concerned about its long-term effects on developing babies. In this case, the mammary gland effects weren't seen until the pups hit puberty. At puberty, estrogen triggers the cells in the ducts of the mammary gland to branch and grow at the terminal end buds. High cell division and death is part of normal growth that stops when the buds reach a certain tissue. During the study, groups of pregnant mice were given either 25 or 250 nanogram BPA per kilogram of body weight per day from the ninth day of pregnancy through four days after they gave birth. Mammary gland development in the female pups was examined at 20 days, 30 days (puberty), and at 4 months of age. TEB properties were similar between experimental and control animals at 20 days. Yet at puberty, those exposed to 250 BPA in the womb had significantly more and a greater area of TEBs relative to the ductal area and had impaired ductal length when compared to controls. Growth-associated cell death was lower in both concentrations, and at four months progesterone receptor expression in cells increased. Based on the results, researchers believe BPA raises a cell's response to estrogen and propels progesterone receptor activity that spurs ductal branching. Further studies are underway to better understand the growth-promoting effects seen in the animals long after exposure to the BPA levels encountered in everyday life. The findings are important because they "suggest that perinatal exposure to BPA in particular, and to estrogens in general, may increase susceptibility to breast cancer." http://endo.endojournals.org/cgi/content/abstract/en.2005-0 340v1 Frog intersex trends mimic chemical use history During the past 150 years, the rise and fall of industrial chemical use coincided with the rise and fall of hermaphrodism in Illinois's cricket frogs. The hydrocarbons and organochlorines accompanying widespread industrialization probably contributed to frog intersex, a lower number of females, and eventual population decline because of the chemicals' masculanizing effects, according to research published in the March issue of Environmental Health Perspectives. The greatest proportion of frogs with male and female gonads (known as intersex) occurred during the time when the insecticide DDT was introduced and industrialization was rampant. Intersex numbers dropped as organochlorines and DDT were banned. Cricket frogs remain one of the most common frogs in Illinois, but like other amphibians worldwide, their numbers are declining, especially in the north where they are rarely seen today... http://ehp.niehs.nih.gov/docs/2004/7276/abstract.html http://ehp.niehs.nih.gov/members/2004/7175/7175.html Signaling through cell membranes Researchers have found another way environmental estrogens interfere with the sensitive hormone signals that control development and reproduction. Some xenoestrogens can jumpstart the chemical signaling systems in a cell via estrogen receptors in the cell's membrane, a recent study confirms. In some cases, very low doses triggered rapid - within 3 to 30 minutes - cell responses similar to estrogen. These findings contrast the typically higher doses and longer time (hours to days) needed for compounds to bind receptors in the cell's nucleus and alter gene activity. The results, published in the November 2004 issue of Environmental Health Perspectives could explain how small doses of compounds act as endocrine disrupters and possibly affect animal and human reproduction. Authors Nataliya N. Bulayeva and Cheryl S. Watson measured the response of kinase enzymes, molecules that help signal hormone actions, in rat pituitary cells after exposing the cells to the potent estrogen estradiol; the organophosphate pesticides dieldrin, endosulfan, and DDE; the plastic ingredients bisphenol A and p-nonylphenol; and the phytoestrogen coumestrol. All compounds, except bisphenol A, quickly sparked kinase activity at low concentrations (nanomolar, 10-9 M). Coumestrol, nonylphenol, and endosulfan, like estrogen, were also active at very low levels (subpicomolar, 10-14 M). But each compound was unique in its reaction time, concentration needed, the pathway affected, and the end points. Therefore, the authors suggest testing compounds for a number of mechanisms in a variety of tissues. http://ehp.niehs.nih.gov/members/2004/7175/7175.html Birth control for fish populations, too A multigenerational laboratory study finds zebrafish offspring exposed through life to similar levels of ethinylestradiol (EE2, the main estrogen in birth control pills) found in waterways produced fewer eggs, no expressible semen, and no offspring due to nonfunctional and abnormal gonads. The fish retained challenging and defensive mating behaviors, though. Researchers speculate that the physical is more prone to disruption than behavior and the altered reproduction and breeding may affect populations. Jon P. Nash and colleagues report their results in the December 2004 issue of Environmental Health Perspectives... http://ehp.niehs.nih.gov/members/2004/7209/7209.html |
|
Archived Briefs 2004 Animals act up Do endocrine disrupting chemicals (EDCs) affect how animals act? Yes, according to two articles published in the October issue of Animal Behaviour. Chemicals such as DDT and PCBs can alter in a number of ways the hormone, nervous, and immune systems that dictate behaviors associated with reproduction, motivation, signaling communication, and social standing... Zala, SM and DJ Penn. 2004. Abnormal Behaviours Induced by Chemical Pollution: A Review of the Evidence and New Challenges. Animal Behaviour. 68(4): 649-664. more... Clotfelter, ED, AM Bell, and KR Levering. 2004. The Role of Animal Behaviour in the Study of Endocrine-disrupting Chemicals. Animal Behaviour. 68(4): 665-676. more... Manure riddled with estrogen The 10 million dairy cows and 43 million pigs in the United States create a lot of estrogen-laden manure every day. Most of it is held in a variety of storage structures before it is spread on fields as fertilizer, which introduces estrogens to soil and water with uncertain effects. Yet, the amount of natural estrogens reaching the environment from these sources is largely unknown making it difficult to predict waterways most at risk. To investigate, researchers measured three natural estrogens - 17-beta-estradiol, 17-alpha-estradiol, and estrone - in a variety of manure holding pits and ponds at 8 dairy farms and 11 swine facilities in the southeastern United States... http://pubs3.acs.org/acs/journals/doilookup?in_doi=10.1021/es0353208 Drug, chemical boost hormones A popular drug and an industrial chemical can interfere with hormone signals and raise cell activity to unhealthy levels, according to research published in the May 4 Proceedings of the National Academy of Science. The effect may be accentuated in women who take estrogen-containing drugs such as oral contraceptives or hormone replacement therapy. The two short-chain fatty acids (SCFA) studied enhance the actions and effects of steroid hormones, such as estrogen and progesterone, by altering different signaling processes that control genetic transcription rates. Enhancing transcription increases a hormone's effects and might lead to illness including reproductive cancers, miscarriage, or polycystic ovaries... http://www.pnas.org/cgi/content/abstract/101/18/7199 Compounds target different signals and synergize In the world of chemical mixtures, one plus one does not always make two. Sometimes, synergy happens and two compounds' combined effects are greater than each compound's individual effects added together. Little is known about how synergy occurs or how to predict these interactions even though we are all exposed to a rich chemical mix in our bodies and in the environment. Now, new research clearly shows synergy is possible when two endocrine disrupters interfere with different hormonal signaling processes during development. Predicting when the greater-than-additive combined effects occur was possible using a mathematical model. To determine individual and combined effects, researchers exposed developing embryos of the small crustacean Daphnia magna to varying levels and mixtures of fenarimol and testosterone – compounds that attack different stages of the water flea's hormone system. Alone, fenarimol, an agricultural fungicide, slows the crustacean's production of ecdysteroid hormones producing late stage developmental effects such as curved spines and deformed antennae. Testosterone, a steroid hormone, binds and blocks ecdysteroid hormone receptors producing both early and late stage developmental effects. Together, the compounds were more toxic during late stage development than would be expected based on the effects of the individual compounds... http://etc.allenpress.com/entconline/?request= get-abstract&issn=0730-7268&volume=023&issue=04&page=1085 PCBs influence heart disease risk factors Exposure to PCB 126, an organochlorine, produces high blood pressure and bigger hearts – factors that increase heart disease risk. Estrogen was not necessary for most effects of PCB 126, a dioxin-like, anti-estrogenic compound. Many factors - high blood pressure, high cholesterol, smoking, diabetes, and a large heart - raise the risk of heart disease, which is a major cause of death in industrialized countries... http://www.sciencedirect.com/ Gators in polluted water have denser bones Female alligators living in a polluted Florida lake have denser bones than those living in an uncontaminated lake supporting previous rodent studies that link environmental estrogens with altered bone structure, according to research published in the March issue of Environmental Health Perspectives. This is the first study to show bone changes in wild reptiles exposed to estrogenic contaminants and illustrates that endocrine disrupting effects are not limited to certain tissues or systems but may alter all parts controlled by steroid hormones... http://ehp.niehs.nih.gov/docs/2003/6524/abstract.html Review finds fetus and newborns at most risk Do environmental chemicals affect human reproductive health? A lack of concrete evidence, a limited understanding of potential risk, and a multitude of confounding and constantly shifting diet and lifestyle patterns still cloud the issue, report the authors of a short review in the British Medical Journal. Richard Sharpe and Stewart Irvine explain that this uncertainty polarizes opinions with some declaring all synthetic chemicals must be banned and others contending that none cause harm. The public's focus on pesticides as the biggest culprits may miss the mark as synthetic chemicals in everyday products (such as phthalates) leach out and pose low-level but more constant and mixed exposures that, so far, have mostly unknown health risks... http://bmj.bmjjournals.com/cgi/content/full/328/7437/447 Feedlot effluent on fish Fish living downstream from cattle feedlots are hormonally imbalanced and physically altered possibly from a mix of synthetic and natural hormones excreted from the bovines, according to a pair of research papers published online in the journal Environmental Health Perspectives. For the first time, feedlot effluent is shown to affect reproductive and endocrine systems of wild fish living in streams containing a mix of hormones, the authors of the companion studies report... http://ehp.niehs.nih.gov/members/2003/6590/6590.html http://ehp.niehs.nih.gov/members/2003/6591/6591.html |
|
Archived Briefs 2003 Flavone and isoflavone phytoestrogens are agonists of estrogen-related receptors While estrogen-related receptors (ERR, ERRß, and ERR) share a high amino acid sequence homology with estrogen receptors (ERs), estrogens are not ligands of ERRs. Structure-function studies from this and other laboratories have revealed that ERRs have small ligand-binding pockets and have provided evidence to show that these receptors can activate gene transcription in a constitutive manner... http://mcr.aacrjournals.org/cgi/content/abstract/1/13/981?etoc Developmental diethylstilbestrol (DES) exposure reveals novel genetic pathways of uterine cell fate determination Oligo-based gene array results showing the changes in expression between DES- and oil-treated uterine samples (DES/oil). Total RNA isolated from DES- or oil-treated mice was subjected to gene Array analysis according to the Affymetric GeneChip Expression Analysis Technical Manual (see Material and Methods). In this table, the signal intensities of the DES- and oil-treated samples are listed. Log ratio indicates the ratio between DES and oil samples (DES/oil), this was further converted to actual “fold change”. In the “change” column, “D” denotes decrease meaning signals in DES-treated samples are decreased compared to oil control samples, whereas “I” denotes increase. The genebank accession numbers and the names of the genes are also listed. BPA, NP: Antiandrogens, Too? Two endocrine disrupting chemicals (EDCs) known for their estrogenic action are also potent antiandrogens - substances that block androgen action. Androgens are steroid hormones, such as testosterone, that mainly control male traits. They bind to androgen receptors (AR) in a cell, move into the cell's nucleus, and combine with DNA to initiate genetic transcription that leads to androgens bodily effects... http://toxsci.oupjournals.org/cgi/content/abstract/75/1/40 PCBs change ER-beta mix in rat brains Exposure to a PCB mixture during a crucial brain development stage in rats permanently changed the number and distribution of estrogen receptor beta (ER-beta) expressing cells in an area of the brain that is critical for female reproduction. The changes in ER-beta numbers may alter reproduction in animals, and possibly humans, exposed to similar levels during early development. This may happen because hormones and some endocrine disrupting chemicals (EDC) bind to estrogen receptors and initiate the genetic messages that dictate reproductive processes... http://ehpnet1.niehs.nih.gov/docs/2003/6126/abstract.html Low dose effects: Undertested, misapplied, misunderstood Low dose effects of endocrine disrupting chemicals (EDCs) - that small, environmentally relevant doses of EDCs have biological effects - remains a contentious issue after years of research and a 2001 National Toxicology Program report finding contradictory evidence for the idea (Environmental Health Perspectives, April 2002). Now, researchers present a solid outline of why low-dose effects are possible and probable and why traditional toxicology testing misses or "dramatically underestimates bioactivity" (i.e., linear and monotonic dose-response curves, lack of thresholds). Using the natural hormone estrogen and its binding interaction with the estrogen receptor in a cell's nucleus as a model, the authors' review how dose, receptor occupancy, and biological response are related and interconnected... http://ehpnet1.niehs.nih.gov/docs/2003/5494/abstract.html Environmental pollutants pose breast cancer risk Breast cancer is the most common cancer in women and one of the most studied. Nonetheless, little is definitively known about its etiology and risk factors, especially those related to hormonally active compounds (or endocrine disrupting chemicals). Background analysis of incidence and mortality trends; studied risk factors (reproductive, pharmaceutical hormones, diet, radiation, and socioeconomic status); animal study conclusions; human epidemiology evidence (occupational and population studies); and research challenges and priorities are offered in this lengthy review... http://ehpnet1.niehs.nih.gov/docs/2003/6310/abstract.html Estrogen found in oceans Sewage may be the major source of estrone - a type of estrogen - found in tropical coastal waters of the Atlantic, Caribbean, and Pacific oceans, report scientists in the April issue of Environmental Health Perspectives. The highest concentrations of the natural steroid were found in water samples taken near sewage outfalls and underground injection wells that leach treated sewage into marine waters. This proximity suggests the most likely source of the hormone is from excreted pharmaceuticals such as birth control pills and hormone replacement therapies. One-half to two-thirds of the estrone found was conjugated, or in an inactive form. Although estrogens excreted from humans are usually inactive and easily dissolve in water, bacteria in the sewage, water, and sediments can convert them into active forms (unconjugated) possibly supplying a constant source of estrogen in oceans... http://ehpnet1.niehs.nih.gov/docs/2003/5233/abstract.html Hypoxia: New endocrine disrupter alters fish reproduction Long-term exposure to low oxygen levels in water, known as hypoxia, lowers sex hormone levels and sharply reduces reproductive success in adult carp, according to research published in the March 20 issue of Environmental Science and Technology. The researchers say hypoxia is an endocrine disrupter because it alters testosterone (T), estradiol (E2), and triiodothyronine (T3) levels that then affect gonad growth and development, sperm production/motility, egg production, fertilization, hatching, and larval fish survival. Other physical factors, such as electromagnetic fields and artificial light, and many synthetic chemicals and natural compounds are known to disrupt the hormone system in wildlife and laboratory animals... http://pubs3.acs.org/acs/journals/doilookup?in_doi=10.1021/es0258327 http://pubs.acs.org/subscribe/journals/esthag-w/2003/mar/science/os_fish.html http://www.sciencenews.org/20030301/fob3ref.asp Two-parter discusses pharmaceuticals and personal care products New analytical methods and increased testing reveal that drugs and health products are a significant source of environmental pollution, especially in waterways. These pharmaceutical and personal care products (PPCP) enter the environment either directly via garbage or drain disposal or indirectly after use through human sewage or runoff from animal holding facilities. Many are estrogenic, androgenic, or some other type of endocrine disrupter. A two-part article, published online in December 2002 and slated for a 2003 publication in the journal Environmental Health Perspectives, is one of the first attempts to comprehensively address the environmental stewardship (prevention, control, and minimization) of PPCP pollution. The papers summarize the problems surrounding PPCP pollution and suggest ways to reduce the contamination associated with the use and disposal of these products by consumers and the health care industry. The pollution prevention strategies target community involvement, voluntary solutions, and regulatory actions with little emphasis on waste treatment. The papers provide a starting point for discussions of future research and prevention actions. Links to the preliminary version of this two-part paper about life cycle control of PPCPs are available at http://www.epa.gov/nerlesd1/chemistry/pharma/overview.htm. Abstract: http://ehpnet1.niehs.nih.gov/docs/2003/5947/abstract.html PDF: http://www.epa.gov/nerlesd1/chemistry/health/ehp5947-1.pdf Abstract: http://ehpnet1.niehs.nih.gov/docs/2003/5948/abstract.html PDF: http://www.epa.gov/nerlesd1/chemistry/health/ehp5947-2.pdf Combination HRT increases breast density - a known breast cancer risk Another study suggests the combination estrogen/progestin used in hormone replacement therapies (HRT) in the United States may pose a health risk. In this study, women given different regimes of the dual hormone therapy had a 3 to 5 percent increase in breast density, a significantly greater density than women taking only estrogen. Greater tissue density is a high risk factor for breast cancer and has been associated - although not quanitated - with combination HRT. The 571 women aged 45-64 participated for a year and took either a placebo, estrogen alone, estrogen and medroxyprogesterone acetate for half a month, estrogen and medroxyprogesterone acetate daily, or estrogen and micronized progesterone for half a month. Mammograms taken before the study were compared to those taken after 12 months of HRT. The authors conclude that estrogen-progestin therapy, but not estrogen-only use, is associated with increases in breast density. (Greendale, G.A. et al. 2003. Postmenopausal hormone therapy and change in mammographic density. Journal of the National Cancer Institute, 95(1):30-37; and Randal, J. et al. 2003. NIH workshop tries to create consensus on HRT use. Journal of the National Cancer Institute, 95(1):9-11.) Removing estrone from water Hormones and pharmaceuticals in sewage outflow can pollute waterways and affect aquatic organisms. One way to prevent compounds from entering the environment is to trap them with membrane filters. In this study, the relative merits and effectiveness of several nanofiltration and reverse osmosis membranes were tested with the estrogen estrone for size and absorption properties under various water conditions. While some membranes retained estrone, the results are variable and depend on surface absorption and water chemistry. (Schäfer, A.I., L.D. Nghiem, and T.D. Waite. 2003. Removal of the natural hormone estrone from aqueous solutions using nanofiltration and reverse osmosis. Environmental Science and Technology. 37(1): 182-188.) Trenbolone steroid has androgenic activity (Wilson, V.S. et al. 2002. In vitro and in vivo effects of 17 B-Trenbolone: A feedlot effluent contaminant. Toxicological Sciences. 70: 202-211.) |
| Archived Briefs 2002 DDT triggers transcription without receptor One way estrogen and estrogen-like compounds - like the organophosphate pesticide DDT and its metabolites DDD and DDE - produce effects is by binding to receptors and activating gene transcription. However, estrogen may also use other avenues - such as activator proteins - that bypass estrogen receptors. In this study, researchers tested for activator protein-1 pathways using altered estrogen responsive and estrogen unresponsive endometrial cancer cells. Although DDT, DDD, and DDE all activated the AP-1 transcription factor without using an estrogen receptor, DDT and DDE were the most potent and stronger effects were seen in the estrogen unresponsive cells. Frigo, DE et al. 2002. DDT and its metabolites alter gene expression in human uterine cell lines through estrogen receptor-independent mechanisms. Environmental Health Perspectives, 110(12): 1239-1245, (Online 28 Oct 2002. ) http://ehpnet1. niehs. nih. gov/docs/2002/110p1239-1245frigo/abstract. html Dioxin reduces immune factors Twenty years after a factory exploded near Seveso, Italy, spewing a dioxin-laden chemical cloud, researchers compared immunoglobulin (an immune protein with antibody activity) and plasma levels in 62 blood samples from people in the most exposed areas with 58 samples from people in uncontaminated areas. As dioxin levels rose in blood samples of those in the most contaminated areas, immunoglobulin G levels decreased indicating dioxon may impact immune system factors and possibly its function. Baccarelli, A et al. 2002. Immunologic effects of dioxin: new results from seveso and comparison with other studies. Environmental Health Perspectives, 110(12):1169-1173, (Online 27 Sep 2002. ) http://ehpnet1. niehs. nih. gov/docs/2002/110p1169-1173baccarelli/abstract. html |
|
Archived Briefs 2001 Nagler, JJ, J Bouma, GH Thorgaard, and DD Dauble. 2001. High incidence of a male-specific genetic marker in phenotypic female chinook salmon from the Columbia River. Environmental Health Perspectives, 109(1):67-69. LaKind, JS, CM Berlin, and DQ Naiman. 2001. Infant exposure to chemicals in breast milk in the United States: What we need to learn from a breast milk monitoring program. Environmental Health Perspectives, 109(1):75-88. What kind and what amounts of chemicals are transferred from mothers to infants via breast milk? Unfortunately, the scant data available from the US on chemical levels in human breast milk and elimination rates from the mother make the article's findings limited and inconclusive. The authors lament this lack of data and recommend a breast milk monitoring program to gather sufficient data "to assess infant exposures during breast-feeding and develop scientifically sound information on benefits and risks of breast-feeding in the United States." Oberdörster, E and AO Cheek. 2001. Gender benders at the beach: Endocrine disruption in marine and estuarine organisms. Environmental Toxicology and Chemistry, 20(1):23-36. This review covers "basic endocrinology of marine and estuarine invertebrates and vertebrates, methods for detecting endocrine disruption, and examples of endocrine disruption in various species." Animal groups covered include the invertebrates crustacea, mollusks, and echinoderms and the vertebrates fish, reptiles, and mammals. The authors conclude that even though more is known about endocrine disruption in terrestrial and freshwater environments than is known for marine and estuarine environments, there is strong evidence for endocrine disruption in marine and estuarine gastropods, mollusks, crustaceans, and fishes. Current scientific challenges include a greater understanding of basic endocrinology, especially of the invertebrates; identifying and analyzing hormonal function in at-risk populations; and suggesting land and water use changes to minimize risks to marine and estuarine populations. |
|
Archived Briefs 2000 Nagler, JJ, J Bouma, GH Thorgaard, and DD Dauble. 2001. High incidence of a male-specific genetic marker in phenotypic female chinook salmon from the Columbia River. Environmental Health Perspectives, 109(1):67-69. Thiruchelvam, M, EK Richfield, RB Baggs, AW. Tank, and DA Cory-Slechta. 2000. The nigrostriatal dopaminergic system as a preferential target of repeated exposures to combined paraquat and maneb: Implications for Parkinson's disease. Journal of Neuroscience, 20(24):9207-9214. Kaufman, RH, E Adam, EE Hatch, K Noller, AL Herbst, JR Palmer, and RN Hoover. 2000. Continued follow-up of pregnancy outcomes in diethylstilbestrol-exposed offspring. Obstetrics and Gynecology,96(4):483-489. Women exposed to deithylstilbestrol (DES) in their mother's womb, so-called DES daughters, have less successful births than unexposed women, according to this recent study. Questionnaires were returned from 3,373 DES daughters registered in the National Collaborative Diethylstilbestrol Adenosis cohort and the Chicago cohort and 1,036 nonexposed women in a comparison group. The study's results suggest that DES daughters are less likely to have full-term live births (64 percent versus 84. 5 percent for unexposed women) during their first pregnancy. When all of a women's pregnancies are analyzed, the DES-exposed are still more likely to have premature births (19. 4 percent versus 7. 5 percent for unexposed), spontaneous abortions (more for exposed women during first trimester and 6. 3 percent for exposed versus 1. 6 percent for unexposed during second trimester), and ectopic pregnancies (at least one more often than unexposed) than unexposed women. These results suggest that potent estrogenic chemicals such as DES can have long-lasting reproductive health effects in humans exposed in utero. LaKind, JS, CM Berlin, and DQ Naiman. 2001. Infant exposure to chemicals in breast milk in the United States: What we need to learn from a breast milk monitoring program. Environmental Health Perspectives, 109(1):75-88. What kind and what amounts of chemicals are transferred from mothers to infants via breast milk? Unfortunately, the scant data available from the US on chemical levels in human breast milk and elimination rates from the mother make the article's findings limited and inconclusive. The authors lament this lack of data and recommend a breast milk monitoring program to gather sufficient data "to assess infant exposures during breast-feeding and develop scientifically sound information on benefits and risks of breast-feeding in the United States." Oberdörster, E and AO Cheek. 2001. Gender benders at the beach: Endocrine disruption in marine and estuarine organisms. Environmental Toxicology and Chemistry,20(1):23-36. This review covers "basic endocrinology of marine and estuarine invertebrates and vertebrates, methods for detecting endocrine disruption, and examples of endocrine disruption in various species. " Animal groups covered include the invertebrates crustacea, mollusks, and echinoderms and the vertebrates fish, reptiles, and mammals. The authors conclude that even though more is known about endocrine disruption in terrestrial and freshwater environments than is known for marine and estuarine environments, there is strong evidence for endocrine disruption in marine and estuarine gastropods, mollusks, crustaceans, and fishes. Current scientific challenges include a greater understanding of basic endocrinology, especially of the invertebrates; identifying and analyzing hormonal function in at-risk populations; and suggesting land and water use changes to minimize risks to marine and estuarine populations. Larsson, DGJ, H Hällman, and L Förlin. 2000. More male fish embryos near a pulp mill. Environmental Toxicology and Chemistry,19(12):2911-2917. Pregnant female fish living within 2 kilometers (km) of a large Swedish pulp mill had significantly more male embryos than their counterparts living farther away from the pulp mill. Researchers sampled 3,423 embryos from 99 female eelpouts ( Zoarces viviparus ) and determined sex by examining the embryos' gonads. The four reference sites had 50 percent females while the two experimental sites closest to the mill had 42 (1. 7 km north) and 45 (1. 2 km south) percent female embryos. A sex ratio shift could skew future eelpout populations and affect the ecosystem since these fish are a main species. The researchers suggest the male-biased shift may be due to endocrine disrupting chemicals from the mill rather than temperature, pH, food, or social conditions. Diana, SG, WJ Resetarits, Jr., DJ Schaeffer, KB Beckmen, and VR Beasley. 2000. Effects of atrazine on amphibian growth and survival in artificial aquatic communities. Environmental Toxicology and Chemistry,19(12):2961-2967. Atrazine at 200 to 2000 micrograms per liter (µg/l) adversely affected water plants and larval frogs living in constructed ponds. The plants were virtually wiped out, while the frogs were shorter and weighed less than frogs exposed to lower concentrations of the herbicide. Frogs in the highest concentration group also took longer to mature than frogs in the 200 µg/l pond. Four ponds were constructed; stocked with plankton, water plants, and larval gray tree frogs ( Hyla veriscolor ); and treated with 0, 20, 200, or 2000 µg/l of atrazine. In the two ponds with the most atrazine, the water's oxygen levels and pH dropped dramatically within one day, increased for several days then dropped again to even lower levels until the end of the experiment. Phytoplankton densities dropped initially in the two most concentrated ponds then rebounded to significantly higher levels than the control pond. Plant life was most affected by the herbicide with a 30, 98, and 99 percent loss in the 20, 200, and 2,000 µg/l treatment ponds respectively. The herbicides intermittent effects on the plants may indirectly affect amphibian growth and stamina, reducing survival and leading to the recently reported population declines, suggest the study's authors. Hiromi Ohtani, Ikuo Miura, and Youko Ichikawa. 2000. Effects of dibutyl phthalate as an environmental endocrine disruptor on gonadal sex differentiation of genetic males of the frog Rana rugosa. Environmental Health Perspectives, 108 (12):1189 - 1193. Developing male tadpoles exposed to the estrogen 17ß-estradiol and the estrogenic substance dibutyl phthalate produced ovaries instead of testes. The genetically male tadpoles exposed to 0. 01, 0. 1, and 1 micromolar estrogen caused 18, 63, and 100 percent of the gonads to develop into complete or partial ovaries. Those exposed to 0. 1, 1, and 10 micromolar dibutyl phthalate caused 0, 7, and 17 percent of the gonads to develop into complete or partial ovaries. Even though dibutyl pthalate is 1,000 times less potent than estrogen, it can alter and affect sexual maturation in developing tadpoles and should be considered an environmentally dangerous substance, say the study's authors. Nynke Weisglas-Kuperus, Svati Patandin, Guy A. M. Berbers, Theo C. J. Sas, Paul G. H. Mulder, Pieter J. J. Sauer, and Herbert Hooijkaas. 2000. Immunologic effects of background exposure to polychlorinated biphenyls and dioxins in Dutch preschool children. Environmental Health Perspectives, 108 (12):1203 - 1207. Exposure to PCBs before birth could alter a child's immune system making them more susceptible to infectious disease and less likely to develop allergies, concludes this new study. Blood and breast milk samples from 207 mother-infant pairs were used to estimate prenatal PCB and dioxin exposure in the infants while blood samples estimated current amounts in the 3. 5-year-old children. Prenatal PCB exposure was associated with less shortness of breath. Current PCB amounts in the children were associated with more recurrent ear infections and chicken pox and less allergic reactions while a higher dioxin burden was associated with more coughing, chest congestion, and phlegm. Health effects from exposure to PCBs and dioxins after birth persist into childhood, say the authors. The PCB exposure seems to increase the likelihood of infectious diseases in young children, which in turn, may lower development of allergies. Sower, SA, KL Reed, and KJ Babbitt. Limb malformations and abnormal sex hormone concentrations in frogs. Environmental Health Perspectives, 108(11):1085-1090. (Online 25 October 2000). Malformed frogs have significantly lower levels of important reproductive and developmental hormones than their normal counterparts, new research shows. These findings suggest environmental contaminants may be an important factor in frog deformities and declining amphibian populations. An exact cause for these far-reaching, worldwide problems is unclear but research has focused on chemicals, parasites, and radiation. In this study, 13 of 16 sites sampled in New Hampshire had malformed frogs. Hormone analysis showed normal frogs produce almost three times more androgen in the gonads and gonadotropin-releasing hormone (GnRH) in the brain than frogs with limb deformities. Reproduction depends on androgens, sex-steroid hormones, and GnRH, a brain hormone that stimulates release of vital reproductive hormones in vertebrate glands. Since the frogs' physical abnormalities occur during development, the researchers propose "environmental factors or endocrine-disrupting chemicals that may cause developmental abnormalities also act during early development to ultimately cause abnormally reduced GnRH and androgen production in adult frogs." For more see UNH Study reveals that environmental pollution could be a leading cause of frog deformities and declining populations.Takahashi, O and S Oishi. Disposition of orally administered 2,2-Bis(4-hydroxyphenyl)propane (Bisphenol A) in pregnant rats and the placental transfer to fetuses. Environmental Health Perspectives, 108(10):931-935. (Online 12 September 2000). Bisphenol A can cross the placenta from mother to baby exposing fetuses to this endocrine disrupting compound. Researchers found that 1 gram/kilogram of 2,2-bis(4-hydroxyphenyl)propane eaten by pregnant rats is readily absorbed and travels rapidly to the mothers' internal organs and the fetuses taking only 20 minutes to reach its highest levels in both. The BPA levels gradually decreased and were 2 to 5 percent of the maximum after 6 hours. For more see Josephson, Julian. Breaching the placenta. Environmental Health Perspectives, 108(10):468Swan, SH, EP Elkin, and L Fenster. The question of declining sperm density revisited: An analysis of 101 studies published 1934-1996. Environmental Health Perspectives, 108(10):961-966. Blount, BC, MJ Silva, SP Caudill, LL Needham, JL Pirkle, EJ Sampson, GW Lucier, RJ Jackson, and JW Brock. Levels of seven urinary phthalate metabolites in a human reference population. Environmental Health Perspectives, 108(10):979. Urine samples from 289 adults show humans are exposed to several phthalates that have unknown health risks. Women of childbearing age had the highest levels of monobutyl phthalate, a reproductive and developmental toxin in rodents, of all age and gender groups. The researchers used a technique that directly measures the phthalate metabolites responsible for animal reproductive and developmental problems. They suggest broadening the number and kinds of phthalates US government agencies are examining for health risks to include diethyl, dibutyl, and benzyl butyl phthalates. Payne, J, N Rajapakse, M Wilkins, and A Kortenkamp. Prediction and assessment of the effects of mixtures of four xenoestrogens. Environmental Health Perspectives, 108(10):983-987. Mixing the estrogenic substances o,p'-DDT, genistein, 4-nonylphenol, and 4-n-octylphenol together and testing them in a yeast estrogen assay produced additive effects. The authors promote the models they used as "useful tools for the assessment of combination effects of multiple mixtures of xenoestrogens." H. Wang, H. Eriksson, and L. Sahlin. 2000. Estrogen receptors alpha and beta in the female reproductive tract of the rat during the estrous cycle. Biology of Reproduction, 63(December):1331-1340. Nadal, A, AB Ropero, O Laribi, M Maillet, E Fuentes, and B Soriaand. 2000. Nongenomic actions of estrogens and xenoestrogens by binding at a plasma membrane receptor unrelated to estrogen receptor alpha and estrogen receptor beta. Proceedings of the National Academy of Science, 97(10 October):11603-11608. Xenoestrogens, like estrogen, are attracted to and can bind to hormone binding sites on a cell's membrane initiating different cellular actions than when they bind to estrogen receptors. Binding to membrane sites triggers rapid molecular actions inside cells rather than the slower, genetic transcription that occurs when binding to estrogen receptors inside a cell's nucleus. In this study, the compounds attached to membrane receptors on pancreatic cells and initiated fast, cellular actions similar to those induced by adrenaline and similar hormones. Guo, YL, P-C Hsu, C-C Hsu, and GH Lambert. 2000. Semen quality after prenatal exposure to polychlorinated biphenyls and dibenzofurans. The Lancet, 356(7 October):1240-1241. The sperm of Taiwanese men exposed before birth to tainted cooking oil are deformed, have reduced movement, and have reduced ability to penetrate developing hamster egg cells, say researchers. The mothers of the 12 men sampled were pregnant and were among many in central Taiwan who were poisoned in 1979 after eating cooking oil tainted with polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans. Questions remain whether these sperm abnormalities will affect fertility and whether lower, background levels of these persistent chemicals can cause similar sperm problems in the overall population. Tommaso S, A Hafezi-Moghadam, DP Brazil, K Ley, WW Chin, and JK Liao. 2000. Interaction of oestrogen receptor with the regulatory subunit of phosphatidylinositol-3-OH kinase. Nature, 407(September 28):538-541. Estrogen partners with different molecules to produce its varied bodily effects, says new research just published in Nature. The hormone incites a string of chemical reactions that lead to positive cardiovascular effects when it binds to an enzyme outside the cell's nucleus. The end result after estrogen binds to phosphatidylinositol-3-OH kinase (PI(3)K) is an increase in nitric oxide synthase activity in the lining of heart, vessel, and other cardiovascular tissue. Nitric oxide signals smooth muscle, like that found in the heart, to relax, which in turn reduces vessel stress and blood pressure. In contrast, estrogen's reproductive effects occur when it binds to the estrogen receptor inside the nucleus and initiates genetic transcription. Wang, M and FS vom Saal. 2000. Maternal age and traits in offspring. Nature, 407(September 28):469-470. Changing hormone levels in aging females can alter the growth and reproduction of their offspring, researchers find. Young-adult mice pregnant for the first time have higher blood estrogen levels and different testosterone patterns as that of early-adolescent and middle-aged pregnant mice. Offspring of the latter two groups weigh less, reach puberty later, and the males have smaller reproductive organs than offspring of young-adults. Georgi NN, NE Hopkins, S Boue, and WL Alworth. 2000. Interactions of dietary estrogens with human estrogen receptors and the effect on estrogen receptor-estrogen response element complex formation. Environmental Health Perspectives, 108(September):867-872. Plus Dietary Estrogens - Good and Bad, Environmental Health Perspectives, 108(September):A416. Different phytoestrogens, plant compounds that can produce estrogen-like effects, differ in their attraction to estrogen receptors and can change the receptors shape and size once bound. This may be why previous studies show that the plant chemicals, found in foods like soy and vegetables, are double-edged swords. Their properties may protect against cancer and reduce menopausal systems yet they can adversely affect an animal's reproduction. Ivelisse C, D Caro, CJ Bourdony, and O Rosario. 2000. Identification of Phthalate Esters in the Serum of Young Puerto Rican Girls with Premature Breast Development. Environmental Health Perspectives, 108(September):895-900. Puerto Rican girls have the highest rate of premature breast development in the world (7 or 8 per 1,000 girls) with some developing as early as 6 to 24 months old. Researchers think phthlates, not pesticides, may be responsible. Walsh, Lance P., and Douglas M. Stocco. 2000. Effects of Lindane on Steroidogenesis and Steroidogenic Acute Regulatory Protein Expression. Biology of Reproduction, 63(October 1):1024-1033. Lindane, one of the oldest synthetic pesticides, and two of its isomers can adversely affect testosterone production by interfering with a pivotal protein's production and expression inside Leydig cells. Researchers found that the three compounds reduce the amount of steroidogenic acute regulatory protein that is needed to mediate intracellular activity during synthesis of the male hormone. This interference may explain how lindane alters animal reproduction. Nonylphenols: Bennett, ER and CD Metcalfe. Distribution of degradation products of alkylphenol ethoxylates near sewage treatment plants in the lower Great Lakes, North America. Environmental Toxicology and Chemistry, 19(4):784-792, 2000. Breakdown products (nonylphenol, octylphenol, and others) of the alkylphenol ethoxylates found in discharge from sewage treatment plants along Hamilton Harbor and the Detroit River in the lower Great Lakes accumulated in animals close to the sewage plants but did not persist far from the outflow. Researchers found ppb (ng/g) concentrations of the byproducts in caged mussels near the plants but trace levels in water, soil, and animals about 1 kilometer from plants on the Detroit River and a few hundred meters from plants on Hamilton Harbor. Microbes in the environment degrade alkylphenol ethoxylate surfactants into the estrogenic breakdown products. Hale, RC, CL Smith, PO de Fur, E Harvey, EO Bush, MJ La Guardia and GG Vadas. 2000. Nonylphenols in sediments and effluents associated with diverse wastewater outfalls. Environmental Toxicology and Chemistry, 19(4):946-952, 2000. Sewage treatment plants are not the only source of nonylphenols found in waterways. Researchers examined 59 effluents and 75 associated sediments from 69 sites in Virginia, including sewage treatment plants and treated and untreated discharge from government research, military and industrial facilities (textiles, oil/gas, paper recycling, chemical/animal feed/metal manufacturers). While 54% of sediments (11 of 20 sites) next to and 15% of effluents from active sewage treatment plants contained nonylphenol (highest was 12,400 µg/kg), the greatest sediment concentration (14,100 µg/kg) was found next to untreated wastewater from floor drains at a federal aerospace research facility and the largest effuent concentration (6,300 µg/l) was in runoff from a shipyard oil/water separator. Nonylphenol seems to be a common contaminant since it was found in 34 of 75 sediments sampled. Some of the highest sediment concentrations occurred in low flow discharges into small creeks where dilution was minimal. In several locations, the compound was detected in sediments but not in outflow. These factors and other evidence suggest nonylphenols "gmay persist for long periods under some evnironmental conditions." Tyler, CR, N Beresford, M van der Woning, JP Sumpter, and K Thorpe. Metabolism and enviromental degradation of pyrethroid insecticides produce compounds with endocrine activity. Environmental Toxicology and Chemistry, 19(4):801-809, 2000. Breakdown products of widely used pyrethroid insecticides are more potent endocrine disruptors than their parent compounds raising concerns about overall safety of the rapidly degraded parent compounds. Seven parent pyrethroids (permethrin, cypermethrin, allethrin, bioallethrin, fenpropathrin, fenvalerate and cyfluthrin) and three permethrin degradation products (cyclopropane permethrin acid, 3-phenoxybenzyl alcohol, and 3-phenoxybenzoic acid) were tested for estrogenic, antiestrogenic, androgenic, and antiandrogenic activity using recombinant yeast with human estrogen and androgen receptors. Of the parent products, permethrin and fenpropathrin were weakly estrogenic; bioallethrin, allethrin, cypermethrin, and cyfluthrin were antiestrogenic; none were androgenic; and all but flenvalerate had varying levels of antiandrogenic activity. All three breakdown products were estrogenic; 3-phenoxybenzyl alcohol was also antiandrogenic and more potent than permethrin; and cyclopropane permethrin acid and 3-phenoxybenzoic acid were also antiestrogenic with potencies 100- to 1000-fold lower than tamoxifen. Because the breakdown products are more potent than the parent compounds and the parent chemicals varied in source and purity, the researchers suggest the parent compounds were not the major active substances in the samples tested. Metabolism by the yeast and contamination of the purchased chemicals could have introduced other compounds into the testing system. Korte, JJ, MD Kahl, KM Jensen, MS Pasha, LG Parks, GA LeBlanc, and GT Ankley. Fathead minnow vitellogenin: Complementary DNA sequence and messenger RNA and protein expression after 17B-estradiol treatment. Environmental Toxicology and Chemistry, 19(4):972-981, 2000. The enzyme-linked immunosorbent assay (ELISA) is less sensitive but simpler to perform and better for routine screening tests than this newly tested ribonuclease protection assay (RPA). Both detect vitellogenin in male fish and thus indicate exposure to environmental contaminants that activate the estroten receptor. In this study, male fathead minnows were injected with 0. 5 and 5. 0 mg/kg of 17-ßestradiol and were measured for liver vitellogenin mRNA levels (detected at 4 hours, maxed at 48 hours, and persisted for about 6 days) and blood vitellogenin protein (detected at 16 hours, maxed at 72 hours and persisted for at least 18 days). Researchers also sequenced fathead minnow vitellogenin DNA and compared it to other fish species. Padrós J, E Pelletier, S. Reader, and F Denizeau. Mutual in vivo interactions between benzo[a]pyrene and tributyltin in brook trout ( Salvelinus fontinalis ). Environmental Toxicology and Chemistry, 19(4):1019-1027, 2000. Two common pollutants can interact in fish and influence each other's breakdown, storage, and excretion. Tributyltin (TBT), a common, estrogenic antifouling agent ubiquitous in marine environments and found in ship hull paint, inhibits some metabolic activity of benzo[a]pyrene (BaP), a carcinogenic polycyclic aromatic hydrocarbon. Blood, bile and liver samples from brook trout were analyzed 48 hours after being injected with either or both compounds. TBT inhibited certain BaP induced P450 enzyme mediated processes (EROD and CN-ECOD) and formation of BaP metabolites. BaP also unexpectedly influenced TBT metabolism. According to the authors, the results suggest that if metabolic mechanisms are known, it is feasible to predict actions between environmental chemicals in ways similar to approaches used in biomedical toxicology. Bishop, CA, B. Collins, P. Mineau, NM Buress, WF Read, and C Risley. Reproduction of cavity-nesting birds in pesticide-sprayed apple orchards in southern Ontario, Canada, 1988-1994. Environmental Toxicology and Chemistry, 19(3):588-599. During this six-year study, p,p' DDE made up more than 90% of the chemical residue found in tree swallow and eastern bluebird eggs that were exposed to pesticides sprayed on apple trees. The swallow eggs contained between 0. 74 to 3. 47 micrograms/gram (µg/g) of organochlorine compounds while bluebird eggs had between 0. 47 to 106. 3 µg/g. In bluebirds, hatching decreased significantly as pesticide levels increased. Dudley, MW, CQ Sheeler, H Wang, and S Khan. Activation of the human estrogen receptor by the antiestrogens ICI 182,780 and tamoxifen in yeast genetic systems: Implications for their mechanism of action. Proceedings of the National Academy of Science, 97(7):3696-3701, 2000. New research shows that antiestrogens inhibit estrogenic responses by triggering genetic transcription that shuts down human estrogen receptor (ER) actions. It was long thought that antiestrogens displaced or blocked estrogen receptors, tying up the binding sites and prohibiting ER-dependent transcription. Using three different yeast systems, scientists demonstrated that the antiestrogens tamoxifen and ICI 182,780 induced ER activity and transcription at concentrations 15,000-fold higher than estradial. Tamoxifen displaced estradiol from ER while ICI 182,780 increased estradiol binding four times. Each probably acts by binding different parts of the estrogen receptor; tamoxifen at the hormone binding site whereas ICI 182,780 at a different location. Adding coactivator RIP140 (a coactivator assists the receptor in activating genes and transcription), increased transcription for both antiestrogens and estradiol by 30 fold. Lindholst, C, KL Pedersen and SN Pedersen. Estrogenic response of bisphenol A in rainbow trout ( Onchorynchus mykiss ). Aquatic Toxicology, 48(2-3):87-94. Rainbow trout exposed to bisphenol A (BPA) via the water incorporate the substance at varying levels in blood, liver, and muscle depending on exposure concentrations. A dose-response relationship exists between liver BPA concentrations and vitellogenin responses. Groups of 10 fish each were exposed to either 10, 40, 70, 100, and 500 micrograms/liter (µg/l) of BPA and were sampled at 0, 6, and 12 days for blood vitellogenin and at 12 days for liver and muscle to determine internal BPA concentrations. The lower limit of vitellogenin response fell between 40 and 70 µg/l, much higher than previous estimates of 2. 3µg/l published in other scientific papers. Fish exposed to 40, 70, and 100 µg/l had increased vitellogenin production from day 0 to 6 followed by constant or decreasing levels from day 6 to 12 while those exposed to 500 ug/l had a significant increase compared to controls until day 12. All groups had significant amounts of BPA in livers. Fish in the10 and 40 groups had undetectable levels in the muscle while fish in the 70, 100, and 500 groups had average muscle BPA concentrations at day 12 of 0. 25, 0. 22, and 0. 83 µg/g respectively. Dewailly, É, P Ayotte, S Bruneau, S Gingras, M Belles-Isles, and R Roy. Susceptibility to infections and immune status in inuit infants exposed to organochlorines. Environmental Health Perspectives, 108(3):205-211, 2000. Prenatal exposure to p,p' -DDE, hexachlorobezene, and other organochlorines could increase a child's risk for inner ear infections, say researchers who compared the number of infectious diseases in Inuit babies from Nunavik, Artic Quebec, Canada) and exposure to chemicals while in the womb. The most frequent disease for bottle-fed and breast-fed infants at 3, 7, and 12 months was otitis media (inner-ear infections). The risk of contracting the illness increased at 7 months with prenatal exposure to p,p' -DDE, hexachlorobezene, and dieldrin while the risk after a full year and the risk of 3 or more recurrent infections correlated with prenatal exposure to p,p' -DDE and haxachlorobenezene. Edmunds, JSG, RA McCarthy, and JS Ramsdell. Permanent and functional male-to-female sex reversal in d-rR strain Medaka (Oryzias latipes) following microinjection of o,p' -DDT. Environmental Health Perspectives, 108(3):219-224, 2000. Directly exposing fish eggs to a weakly estrogenic substance permanently changes male fish to functioning female fish, possibly altering sex ratios in wild populations. Just fertilized Japanese medaka fish eggs were injected with o,p' -DDT, a process that mimics the natural chemical transfer from mothers to eggs. Only 50% of eggs survived a dose of 511 nanograms/egg (ng/egg) of o,p' -DDT. A dose of 227 ng/egg changed 86% of genetic males (XY chromosomes) into females that retained XY chromosomes and some male pigmentation but had fully functional ovaries. Half of XY females bred to XY males produced viable eggs, a rate similar to normal XX females. Carlson, DB, LR Curtis, and DE Williams. Salmonid sexual development is not consistently altered by embryonic exposure to endocrine-active chemicals. Environmental Health Perspectives, 108(3):249-255, 2000. Although rainbow trout and chinook salmon embryos injected with one or a mixture of chemicals had elevated levels of o,p' -DDE and p,p' -DDE in fat tissue after 6 month, this study found no effect on sex ratio, gonadal histology, sexual development, or gonadal steroid production. Long, X, R Steinmetz, N Ben-Jonathan, A Caperell-Grant, PCM Young, KP Nephew, and RM Bigsby. Strain differences in vaginal responses to the xenoestrogen bisphenol A. Environmental Health Perspectives, 108(3):243-247, 2000. Some rat strains respond differently to bisphenol A (BPA) than others. This paper determines that vaginal tissue in F344 is more sensitive to BPA than vaginal tissue in Sprague-Dawley (SD) rats. Differences in cell differentiation were found when a dose of 37. 5 milligrams/kilograms (mg/kg) body weight of BPA increased vaginal epithelial DNA synthesis in F344 rats but no amount stimulated synthesis in SD rats. Intermediate steps in cell proliferation seem to govern the differences. Early responses, such as BPA's metabolic blood clearance time, its affinity for vaginal estrogen receptors, and its ability to increase mRNA in c-fos gene, were similar in both strains. The authors' believe their findings reinforce the need for caution when determining which endpoints and animal models should be used for testing estrogenic effects of environmental contaminants. McNally, JG, WG Müller, DWalker, R Wolford, and GL Hager. The glucocorticoid receptor: Rapid exchange with regulatory sites in living cells. Science, 287(February 18):1262-1265, 2000. New research showing that activated steroid receptors leave their genetic docking stations once transcription starts contradicts previous beliefs and suggests that receptors may be constantly available for activation. Researchers tagged a glucocorticoid receptor in live mouse cells then watched as the hormone-activated protein migrated to its target gene, turned it on, and then left once the genetic processes began. Scientists previously thought that receptors stayed bound to genes until the genetic processes were complete. Now it appears receptors, even when linked to a hormone, are very active and may function continuously. John, DM, WA House, and GF White. Environmental fate of nonylphenol ethoxylates: Differential adsorption of homologs to componenets of river sediment. Environmental Toxicology and Chemistry, 19(3):293-300. and Topp, E and A Starratt. Rapid mineralization of the endocrine-disrupting chemical -nonylphenol in soil. Environmental Toxicology and Chemistry, 19(2):313-318. These two papers discuss mechanisms of persistence, breakdown, and sediment interactions of nonylphonol polyethoxylates (NPEOs). NPEOs are a mixture of nonionic surfactants used in industry, agriculture, and household products. The substances get into waterways via sewage treatment plants, manufacturing outflows, and runoff. While in transit, the compounds can be degraded, mainly by microorganisms, to shorter, more estrogenic subunits, such as nonylphenols and octyphenols. These substances cling to and aaccumulate in organic matter in sediments. The John et al study established which NPEO subunits congregate in what type of sediment. Longer chained varieties preferred adherring to mineral (inorganic) portions of sediments while the shorter chained, more estrogenic varieties, adherred to organic matter. Even though the compounds accumulated in both fresh and saltwater, high salinity caused particulates to accumulate in the bottom sediments, exposing bottom-dwelling marine organisms, as well as their predators, to these substances. Bioremediation is complicated by this adsorption to different kinds of sediments. Topp and Starratt discovered that the microorganisms that metabolize 4-nonylphenol are found in a variety of soil and temperature types, including loam soils from Ontario and organic and loam soils from the Canadian Far North. Pulgar, R, MF Olea-Serrano, A Novillo-Fertrell, A Rivas, P Pazos, V Pedraza, JM Navajas and N Olea. Determination of bisphenol A and related aromatic compunds released from bis-GMA-based composites and sealants by high performance liquid chromatography. Environmental Health Perspectives, 108(1):21-27, 2000. SE Gruninger, and DM Meyer. Pharmacokinetics of bisphenol A released from a dental sealant. Journal of the American Dental Association, 131:51-58, 2000. Dental composites and sealants kept under controlled pH and temperature leached several different types of bisphenal A (BPA) compounds, say Pulgar et al in their recent paper. These estrogenic compounds were found at environmentally significant levels suggesting a need to examine the relevance to patient care, dentists, and public health. The plastic sealants are used to prevent tooth decay. A major ongoing debate started when research suggested these types of sealants leech BPA compounds before they harden, exposing children and adults to the estrogenic BPA substances. Other research by Fung, et al reports that even though chemicals leech, they are not a health threat because they are absorbed by the body, absorbed at below detection levels, or metabolized immediately. In this research, 8 milligrams of BPA was appliet to either one tooth or four teeth in 40 adults. Significant levels, between the high-dose and the low-dose groups, of BPA (5. 8-105. 6 parts per billion (ppb)) were found in saliva samples at 1 and 3 hours after sealants were applied but 1-, 3-, and 5-day saliva samples had no BPA and none of the blood samples contained BPA. Fung concludes that BPA released orally may not pose a hormone-related health threat because it is either not absorbed or is below detection. BPA found in other commerical sources, such as the lining of food cans, may offer greater exposure and therefore greater risk than dental sealants. |
