Environmental Chemicals and Estrogens
The Good, the Bad and the Unknown. Lessons From Fish
By Sherilyn J. Sawyer
Department of Biology, Boston University
This article is the second in a series "From Research to Real Life" that GBPSR presents in conjunction with the Boston University Superfund Basic Research Program (BUSBRP).
We hope this information encourages you to become more involved in PSR programs or other activities that address preventing toxic exposures that may jeopardize public health.
Today, estrogens are commonly known for their roles in reproduction, hormone replacement therapy, oral contraceptives, and the controversies surrounding breast and other cancers; all focusing on women. Although these "women's issues" have been in the spotlight lately, estrogen has many important roles in the bodies of both women and men.
Estrogens Important to Nervous System of Both Sexes
Recently it has become apparent that estrogens have many functions in the nervous system of both sexes, specifically on areas of the brain important for learning and memory, as well as motor coordination and pain sensitivity. Correlations between gender specific estrogen levels and cognition, depression, Alzheimer's disease, and Parkinson's disease demonstrate the importance of estrogens in neural health. The understanding of normal and abnormal neural estrogen activities and regulation is vital to understanding connections between estrogen, neural development and the maintenance of the nervous system in adults.
Environmental Chemicals as Hormone Disruptors
In general, our bodies are very good at producing just the right amount of hormones and other regulatory molecules, but what if man-made chemical pollutants found in our environment could enter the body and act as hormones, like estrogen, altering the body's innate regulatory mechanisms? This process, termed endocrine disruption, can and does happen. For several decades endocrine disruption has been linked to reproductive abnormalities and to some cancers. But what if there were also less obvious, more subtle effects? For example, could exposure to this type of pollution prenatally alter the mental development of a child? Or could endocrine disruption in development or adulthood change susceptibility to neural disease such as depression, Alzheimer's, Parkinson's, and macular degeneration in advanced age? Our laboratory at Boston University has demonstrated that some pollutants do have an effect on gene regulation in neural tissues and it is our goal to determine how natural estrogens and endocrine disruptor chemicals (EDC) affect the processes of development and aging of the brain.
Estrogen and Gene Expression
Paradoxically, the "female hormone" estrogen is a derivative or the so-called "male hormone" testosterone. In reality, both hormones are present in males and females, just in differing amounts. A process called aromatization, mediated by the enzyme aromatase, drives the production of estrogen from testosterone. Normal levels of neural estrogen play a role in signaling cells during development and potentially throughout life. The process by which estrogen acts in cells is mediated by a protein transcription factor, the estrogen receptor, which binds to estrogen and then exerts an effect on gene expression in the cell. By modulating gene expression, estrogen can subsequently influence the amount and types of proteins within the cell, thereby changing the cell's fate or function. For example, it is cell signaling that directs the developmental timing and formation of the many different neural tissues. Consequently, disruption of these signaling systems can have a wide variety of effects on the outcome of tissue differentiation and development.
Pollutants Can Mimic or Block Hormones
Environmental exposure to compounds that can mimic or block the activities of hormones (endocrine disruptors) is of growing concern. Several known compounds have activity similar to the body's own estrogen. Two common EDC's studied specifically in our lab are PCB's and BPA. Polychlorinated hydroxybiphenyls, or PCBs, are a class of compounds some of which affect estrogen signaling pathways. Until the halt of their U.S. manufacture in 1977, PCB's were commonly used as lubricants and coolants in a wide variety of electrical equipment including common household items. Due to a very long half-life PCBs were found to build up in the environment, specifically in soil, sediment, and water, where they still exist today. Another prevalent environmental estrogen, bis-phenol A or BPA, is a building block of polycarbonate plastics and polystyrene resins. The common plastics made from BPA are found in the lining of metal food cans, in plastic milk, juice and water cartons, in baby bottles, in microwave oven ware, and in other widely used plastic and polystyrene food packages. PCB's and BPA enter the body through exposure to contaminated material, most commonly through ingestion of contaminated foods and water. Once in the body, these compounds and others like them can be circulated, metabolized, and/or stored by the body tissues where their effects can continue for long periods of time.
Lessons from Zebrafish and Killifish
Work in our lab is concerned with estrogen and EDC effects on neural endpoints. In order to study this we use fish as a model system; specifically laboratory raised zebrafish, and the killifish, which is found in the natural environment. The two different fish species allow us to perform year round controlled zebrafish experiments in the lab, and to provide a direct environmental connection by examining what is happening to populations of killifish living in the EDC polluted waters of New Bedford Harbor Massachusetts. As a measure of estrogenic effects, our lab is currently studying the regulation of neural aromatase, the gene responsible for estrogen production in the brain, as well as several members of cell signaling pathways, and neural structural components thought to be targets of estrogen and EDC. To date our work has demonstrated the ability of estrogen and endocrine disruptors to alter gene regulation during development and adulthood using both fish as models in the lab, and by studying natural fish populations. This information is the first step in understanding the normal and abnormal roles of estrogen and EDC in the development and maintenance of neural tissues. In the future we hope to further elucidate the role of endocrine disruption and estrogen pathways in neural health during development and age.
GBPSR serves on the Community Outreach Core of the Boston University Superfund Basic Research Program (BUSBRP), an EPA-funded program to support research into the possible reproductive and developmental effects of chlorinated and non-chlorinated organic chemicals and substances (dioxins, PCBs, some solvents). The goal of the COC is to provide a basis for a new collaborative structure bridging the university with the community in order to, among other things, increase public awareness about environmental health research, and link members of the professional community with academic environmental health research. GBPSR has been working to bring important BU research information to our membership through a variety of mechanisms including articles and presentations.
For more information: http://www.bu.edu/dbin/sph/research_centers/superfund.php