Hormones: "Endocrinology 101"
Hormone are released by various glands throughout the body. They act as chemical messengers guiding vital processes including the regulation of metabolism, reproduction, mental processes, and many aspects of development before birth.
The bodies chemical communications system has two basic components: though hormones themselves and special molecules, known as receptors, that receive the chemical messages. The body has hundreds of different kinds of receptors, each one designed to receive a particular kind of signal.
Each hormone and its particular receptor have a "made for each other" attraction, which scientists call "high affinity". Without hormone and its receptor have a "lock-and-key" relationship. When they encounter one another, they grab hold, emerging as a molecular embrace known as "binding". Once joined, the hormone and molecule and its receptor move into the cells nucleus and trigger though production of particular proteins that "turn on" the biological activity associated with the hormone.
The theory of how the body communicates through hormones has been dominated by this "lock-in-key" theory and the hypothesis that receptors will bind only to their intended hormone or closely related compounds. Nevertheless, reality has proven more complicated and hormones and their receptors appear to behave far more "promiscuously" then theorized.
Disrupting the Body's Chemical Messengers
Over the last decade, we dozens of scientists have studied various ways that the hormone system can be disrupted. On the cellular level, scientists have any good understanding of the various ways that synthetic chemicals can disrupt the chemical message conveyed by hormones. What is not well understood is how certain chemicals act to either disrupt hormones or fool receptors.
Research has shown that many foreign chemicals can bind to the bodies hormone receptors. What puzzle scientists is that on a molecular level some of these chemicals bear little structural resemblance to natural hormones.
Some synthetic chemicals act as hormone impostors by binding to the hormone receptor and inducing a hormonal response. Others act as hormone blockers by occupying the receptor and preventing the bodies own hormone from attaching. Still others help the body eliminate natural hormones more rapidly than they would have been eliminated, or alternatively, too slow their rates of production.
While most of the popular discussion of hormone disruption has focused on synthetic chemicals that mimic or block estrogen, the female hormone, new studies have found that some synthetic chemicals also interfere with androgens, or male hormones. Some studies have found that DDE, a DDT breakdown product still pensive in the environment and human animal tissue, can disrupt hormones levels by accelerating the breakdown and eliminations of steroid hormones from the body.
Contrary to some early suggestions in the literature, synthetic hormone disruptors are not always weak imitators of natural hormones. Some compounds are proving nearly as potent as natural hormones, capable of operating at extremely low concentrations measured in parts per trillion.
Basic Principles of Hormone Disruption:
Observations in the Laboratory and Elsewhere
Because hormones trigger important events before birth, including key steps in sexual development, hormone-disrupting chemicals are a particular hazard to the unborn. They do their damage without altering genes or causing mutations but rather disrupting the expression of genes in the genetic blueprint an individual inherits from his parents.
University of Missouri biologist, Frederick vom Saal, has demonstrated through years of research on mice that tiny shifts in hormones before birth can have consequences that lasted a lifetime. Vom Saal has linked the dramatic differences evident among genetically identical animals to a mouse's position in the womb into the resulting tiny differences in hormone exposure. For example females developing between two males are more aggressive than those developing between other females, less attractive to males, and have shorter reproductive life. Later work found that developing males are also sensitive to slight variations in their prenatal hormone environment and to the tiny amounts of hormones washing over from their utero neighbors.
The tragic episode in medical history involving the synthetic estrogen diethylstilbestrol or DES has demonstrated the dangers of tinkering with hormones levels during pregnancy. It has also demonstrated that at least some animal studies can provide an early warning for humans. Although early research found that giving extra natural or synthetic estrogen to pregnant rats derailed the sexual development of their offspring, doctors prescribe the U.S. from the late 30s to the early '70s to an estimated 5 million pregnant women in the mistaken belief that would help prevent miscarriages and produce healthier babies. Years later, the consequences for the children came to light in the form of rare vaginal cancers, misshapen uteri, and a variety of other reproductive and health problems. The DES experience service as a model of what pollutant hormone disruptors might be capable of doing.
Laboratory research prompted by these discoveries has demonstrated that rodents and humans suffer the same damage to the genitals and reproductive tract from DES and presumably other hormone-disrupting substances. Along with other comparative developmental research, the DES studies have underscored that evolution has determined a basic strategy shared by all vertebrates for embryonic development. Across a wide range of species including humans, hormones regulate development in fundamentally the same way.
The Evidence in Wildlife
Wildlife researchers have been documenting cases of derailed sexual development, abnormal behavior, intersects offspring, impaired fertility, immune system impairment, in abnormal parenting in making behavior in many species including turns and gulls, harbor seals, bald eagles, beluga whales, lake trout, panthers, alligators, and turtles. In many cases, these problems have been linked to hormone-disrupting chemicals.
The alligators in Lake Apopka, one of Florida's largest freshwater bodies, have recently become the most notorious case because their defect is visible and dramatic. Many of the males have tiny penises, an external sign of the largely invisible developmental damage from hormone-disrupting chemicals that has sabotaged the ability of these alligators to reproduce.
Researchers working with North Sea seals correlated high concentrations of endocrine disrupting chemicals with the immune system suppression and reproductive failure.
Wildlife toxicologists Michael Fry has shown that derailed sexual development in bird colonies was caused by hormone disrupter. Though the male birds in these affected colonies looked normal, their sex organs showed a severe sexual confusion. With fewer functional males, females began nesting with females. Friday reproduced the contaminants of facts on the goals sexual organs in the laboratory by injecting gold eggs with the same levels of hormone-disrupting chemicals found in the contaminated colonies.
Some forms of dioxin have been shown in laboratory experiments with rats to alter critical immune system components called T lymphocytes, or "killer cells," and result in a immune system suppression.
Animal studies have shown that even a single, relatively slight exposure to a hormone-disrupting chemical at a critical stage of development can have dramatic and permanent effects on offspring-altering everything from adult male sperm count and Tesco size to mating behavior.
The Human Connection
Tracing cause and effect in humans is extraordinarily difficult because controlled experiments are unethical and contamination patterns in the real world are so highly varied. Whether hormone-disrupting chemicals are now having a broad impact across the human population is difficult to assess due to the nature of the contamination, the transgenerational nature of the effects, the often long lifetime before damage becomes evident, and the invisible nature of much of this damage. In the real world, where humans and animals are exposed could to contamination by dozens of chemicals that maybe working jointly or sometimes in opposition to each other and were timing may be as important as does, meet cause-and-effect linkages will likely remain elusive.
Those trying to document whether perceived increases in specific problems reflect genuine trends in human health also find themselves thwarted by a dearth of reliable medical data. Few diseased registries exist for anything except cancers. While a number of pediatricians from very sparse United States have expressed concern about an increasing frequency of genital abnormal teas in children such as undescended testicles, extremely small penises, and hypospadias (a defect in which to the urethra that carries urine does not extend to the end of the penis), it is virtually impossible to document these anecdotal reports.
In the face of these difficulties, animal studies and unfortunate cases of human exposure to the hormone disruptors can alter us to the probable kinds of effects and help focus research efforts. As a history with DES demonstrates (see above), laboratory experiments with rats accurately forecasted damage that later showed up in humans. What limited research into the human connection there has uncovered possible impacts in humans that are instructive and suggestive.
In July 1991, specialists from a variety of disciplines from toxicology to zoology to immunology shared what they knew about the impacts of hormone disruptors on wildlife, laboratory animals and humans. As the evidence was laid out, the parallels between species proved remarkable. Those attending the meetings issued what is now known as the Wingspread Statement, warnings that the endocrine disrupter threatening the survival of many wildlife populations are also having impacts on humans.
A new consensus statement by a group of leading brain, near illogical, and behavioral researchers will be published spring 1996.
Sperm count studies conducted by a Danish scientific team headed by Dr. Niles Skakkeback and published in the British Medical Journal in September 1992 reviewed 61 scientific studies involving 15,000 men from 20 countries finding that average male sperm counts had dropped 45 percent between 1940 in 1990. Skakkeback, who had been a longtime skeptic of similar sperm count studies, also found that during this period the number of men with extremely low sperm counts increased from 6 to 18 percent.
A Scottish steady conducted by the Medical Research Council's Reproductive Biology Unit to in Edinburgh found lower average sperm numbers and greater numbers of sperm abnormalities in men born in the 1969 vs. men born in 1940.
Belgian researchers, comparing sperm samples from 360 men donated after 1990 with samples donated before 1980, found an alarming increase in unhealthy sperm.
The most recent and perhaps most persuasive study corrects for any variations related to age. In 1992, a team of French scientists led by Jacques Auger confirmed a 50 percent decline in average sperm counts of 30-year-old man born in 1945 (and measured in 1975) and 30-year-old man born in 1962 (and measured in 1992). This and other age controlled studies counter alternative explanations for lowered sperm counts such as adult exposure to contaminants, smoking, and alcohol. The fact that sperm counts correlate inversely with date of birth points directly to the likelihood that the damage occurred in the womb.
Skakkeback has reported a tripling of the incidence of testicular cancer in Denmark.
British researchers report a doubling in the number of cases of undescended testicles between 1962 in 1981. Similar increases have been reported in Sweden and Hungary.
Vom Saal's research with mice found that males exposed prenatally to elevated estrogen levels develop more androgen receptors in their prostates which become permanently sensitized to testosterone and venerable to enlargement. Tufts University scientist Shuk Mei Ho found that long-term exposure to estrogen can produce prostate cancer in rats
The National Cancer Institute reports a 126 percent rise in prostate cancer from 1973 to 1991 (adjusted for age and other demographic effects).
Reproductive Problems in Women
Hormone-disrupting chemicals may play a role in causing tubal or ectopic pregnancies. DES daughters suffer three to five times more tubal pregnancies than unexposed women. A 1990 Wisconsin study reported by the Centers for Disease Control found that the rate of ectopic pregnancies in the state increased 400 percent between 1970 and 1987.
Rates of endometriosis, a disorder driven by hormones and which uterine cells proliferate elsewhere in the body, have soared. Almost 5 million women are affected with this condition which can cause pain and sterility. In a University of Florida study, 79 percent of Rhesus monkeys exposed to dioxin developed that condition. German researchers have found that women with Endometriosis have higher levels of PCBs in their blood than other women.
Breast cancer incidence are up. Lifetime estrogen exposure has been identified by many researchers as a single most important factor for breast cancer.
Research out of Mount Sinai School for Medicine has linked higher rates of breast cancer with high loading of the hormone disruptor DDE. But the results of other studies have been inconsistent. There is a great need for additional research in this area.
Some of the best research on this issue has come from Tufts University medical researchers who have found that certain hormone-disrupting chemicals can cause estrogen sensitive breast cancer cells to proliferate in the laboratory.
Research on the developing brain and nervous system has found that thyroid hormones help orchestrate the elaborate step-by-step process that is required for normal brain development. Research at both Agricultural University of Wageningen in the Netherlands in the University of Illinois has established that the synthetic hormone-disrupting chemicals can affect the thyroid system in complex and has yet incompletely understood ways.
An extensive, long-term study at Wayne State University has found a correlation between exposure of mothers to PCBs and other hormone-disrupting chemicals in Lake Michigan fish and their neurological and cognitive impairment in their children.
Genesis of Our Stolen Future
Although the first scientific report that synthetic chemicals could inadvertently disrupt the endocrine system appeared in 1950, the study between two Syracuse University researchers sank into oblivion and hazard when largely unrecognized for more than three decades. The issue has recently reemerged income to public attention largely through the efforts of Dr. Theo Colborn, a zoologist with the World Wildlife Fund.
Colborn stumbled onto the problems while preparing a report on the bar mental health of Great Lakes in 1987. Although the Lake and many of the bird populations had made a remarkable recovery after environmental laws eliminated the most egregious pollutants, her survey of the scientific literature and conversations with biologists working in a region led to doubt that the lakes were truly "cleaned up" unhatched eggs, mysterious wasting in newly hatched turn chicks, strange crossed bills and other deformities in cormorants, female gulls nesting together, and other wildlife anomalies suggested that something was still seriously wrong.
The breakthrough for Colborn came when she moved beyond the reigning cancer paradigm that had initially blinded her two key clues about the nature of the problem in the Great Lakes. Despite the preoccupation with cancer, humans in the region were not, contrary to public perception, suffering from elevated cancer rates nor was cancer a factor in most of the wildlife problems. Her detective work on wildlife eventually led to two key insights: Although adult animals in many wildlife populations looked normal and healthy, they were having difficulty producing healthy offspring; and while these animals are contaminated with a staggering array of chemicals, many other substances shared the common characteristics of interfering with the hormone system.
Once the Great Lakes study had ended, Colborn continued her investigation into hormone disruptors and their effects. She amassed an extensive database on the suspected chemicals and the problems associated with them. Slowly, with the help of key researchers, Colborn has constructed her endocrine disruption hypothesis which relies on wildlife data, laboratory experiments, and extensive human experience with diethylstilbestrol (DES), and studies on the mechanisms of hormone action. Like Rachel Carson, she has undertaken a vital but often neglected task of synthesizing in analyzing the scientific literature rather than conducting original research.