Part II: The DES Paradigm: Crossing the tolerance threshold
Part I. Introduction
DES Paradigm: Crossing the tolerance threshold
Developed in 1938, DES was commonly prescribed for women with problem pregnancies in the belief that insufficient estrogen levels caused miscarriages and premature births. In the decades that followed, doctors also began to recommend the drug for untroubled pregnancies, as well as for a number of other conditions ranging from acne to prostate cancer. College clinics also doled out DES as a "morning after" contraceptive and farmers used tons of the substance in animal feed to fatten livestock.
Regardless of the compelling association between DES and vaginal cancer reported by the Massachusetts General team, some in the medical and scientific communities remained skeptical that a prenatal exposure to DES could cause cancer. The issue was still unsettled when John McLachlan, a young researcher who specialized in the transfer of drugs and other chemicals into the uterus, arrived at the National Institute of Environmental Health Sciences near Raleigh, North Carolina. In subsequent animal studies, McLachlan and his colleagues demonstrated not only that female mice exposed to DES in the womb eventually developed vaginal adenocarcinoma but also that exposed males turned up with congenital reproductive system problems, ranging from undescended testicles to abnormal sperm to reduced fertility. DES had somehow interfered with hormonal messages during the rodents' prenatal development.
In the years that followed, ample evidence came to light linking DES not only to human vaginal cancer but also to deformities of the reproductive tract. DES daughters have higher than normal chances of miscarriage, ectopic pregnancy, and premature delivery.
How do hormone mimics such as DES disrupt the endocrine system? To act, a hormone must find--and bind with--the appropriate receptors in and on cells. Once joined to the receptor, hormones move into the cell's nucleus, targeting genes that "turn on" the biological activity associated with the hormone. DES binds to estrogen receptors, which are found inside cells in many parts of the body, including the uterus, breasts, brain, and liver.
The synthetic hormone has two troublesome traits. First, it triggers certain parts of the reproductive system more effectively than does estradiol, one of the body's own estrogens. Perhaps even more important, it manages to circumvent a mechanism that protects the fetus from the developmentally disruptive effects of excessive estrogen exposure. Normally, special maternal and fetal blood proteins soak up almost all excess circulating estrogen. But they do not recognize DES. As a consequence, DES in the fetal blood supply remains biologically active.
How many other human-made chemicals act in this way is a major unanswered question. But evidence suggests that, like DES, other compounds can also make end runs around the body's defense mechanisms. If so, the unborn--whether humans or other animals--are vulnerable to disruption from many quarters.
To date, researchers have identified at least fifty-one chemicals--many of them common--that disrupt hormones in one way or another. Some mimic estrogen as DES does, but others interfere with other parts of the endocrine system, such as thyroid and testosterone metabolism. The tally includes large chemical families--the 209 compounds classified as polychiorinated biphenyls (PCBs), the 75 dioxins, and the 135 furans--that have myriad, documented disruptive effects.
One hundred thousand synthetic chemicals are now on the market around the world. Each year about a thousand new substances are introduced, most of them without adequate testing and review. Some that have been found harmful have been withdrawn from use in the United States, but according to U. S. customs export records, analyzed by the Foundation for Advancements in Science and Education, in 1991 the United States exported at least 4.1 million pounds of pesticides that have been banned, restricted, or voluntarily withdrawn from use domestically. Overall, exports included 40 million pounds of compounds known to be endocrine disrupters.
Yearly, five billion pounds of pesticides are applied worldwide, not only to agricultural fields but also in parks, schools, restaurants, supermarkets, homes, and gardens. Although synthetic chemicals now seem an inextricable part of the fabric of modern life, they have only come into use fairly recently.
Now scientists are finding evidence that hormone-disrupting chemicals may have combined effects and that seemingly insignificant quantities of individual chemicals can have a major cumulative effect. The magnitude of this problem is still unknown, but those who have watched the list of hormone disrupters grow think the age of discovery is far from over.
Colborn, T., D. Dumanoski, J. P. Myers. 1996. Hormonal Sabotage. This article and the ones linked to it was originally published in Natural History, March 1996, 105(3):42-49. Excerpted from the book Our Stolen Future.
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