Manufactured from cholesterol by a woman's ovaries each month, the hormone called estrogen circulates in the blood, passes easily in and out of all organs and tissues and is eventually metabolised by enzymes in the liver.
Certain tissues in a woman's body however, contain receptors that latch onto estrogen molecules as they float through her body. During the few hours when estrogen molecules are bound to the receptors, the cells of these "target tissues" are stimulated to proliferate.... The cells of the uterus and the breast all contain large numbers of estrogen receptors. In the presence of estrogen, they grow.
A few years ago, cell biologist Dr. Ana Soto was working out the biochemical details of estrogen sensitivity and its relationship to breast cancer when something puzzling happened in her Tufts University laboratory.
Tissues growing in plastic dishes containing no estrogens started proliferating."This indicated that some type of contamination had occurred, "Soto remembered. "We made an accidental discovery." Soto traced the contamination to the plastic tubes she was using to store blood serum.
Working with her colleague Carlos Sonnenschein, Soto purified the contaminant and identified it as nonylphenol, a chemical added during the manufacture of plastic to prevent it from cracking. They discovered molecules of nonylphenol were being shed from the tubes into the serum.Soto and Sonnenschein went on to prove that nonylphenol is estrogenic - that is, it mimics the effect of estrogen when added to tissues containing estrogen receptors. In a series of experiments published in 1991, Soto demonstrated that human breast tissue proliferates in the presence of nonylphenol, possibly placing it on the path to tumour formation. Soto and Sonnenschein's research is now focused on quantifying the estrigenicity of nonylphenol and other substances.
These chemicals are being termed xenoestrogens: substances foreign to the human body that, directly or indirectly, act like estrogens.
Xenoestrogens are a hot area of research right now. Because of their ability to interfere with the normal process of hormonal regulation in women's bodies, xenoestrogens are being implicated in many reproductive disorders, ranging from infertility and endometriosis to breast and ovarian cancer....And, as increasing numbers of chemicals are demonstrated to function as xenoestrogens, scientists are beginning to learn just how amazingly estrogenic the industrialised world is. Nonylphenol, for example, is not only found in plastic but is also an additive in detergents and pesticides. According to Soto, over 450 million pound on nonylphenols are produced each year. Nonylphenol is also an ingredient in spermicides.The banned pesticide DDT is a xenoestrogen. So is the unbanned pesticide endosulphan. So is atrazine, the most commonly used weed killer in US cornfields. So is DES, the drug given to millions of women from 1948 to 1972 to prevent miscarriages (which it didn't). And so are dozens of different combustion products emitted from coal-burning power plants and automobile exhaust pipes.
To understand the impact of xenoestrogens on women's health - we have discovered through our investigation - one has to become a bit of an endocrinologist, chemist, and historian.
A Pentagon and Three Hexagons
Like all steroid hormones (primarily reproductive related hormones), estrogen has a "backbone" made up of 17 carbon atoms arranged as three hexagons interlocked with a pentagon. Estrogen can exist in one of several modified forms, and each form has its own chemical name. The most potent form produced by the ovaries is called estradiol.Blood levels of estradiol rise steadily during the first half of a woman's menstrual cycle. All cells of the body are permeable to estradiol. However, most estradiol is carried in the blood on special sex-hormone binding proteins. These carrier proteins regulate and slow down the entry of estradiol molecules into surrounding tissues. This feature turns out to be important because many xenoestrogens are not carried on these molecules and can therefore enter cells more quickly and at low concentration.When estradiol enters the cell of a target tissue such as the breast or the lining of the uterus and is bound by an estorgen receptor, the story becomes more mysterious. Just 10 years ago, scientists learned that these receptors are themselves attached to the coiling strands of DNA where our genes lie like beads on a string.
When attached to estradiol, the receptor triggers a change in gene expression. Depending on the type of tissue, some genes may be turned on; different proteins may be manufactured; the rate of cell division may accelerate. The exact mechanisms of action is still an ongoing subject of research. What is known for sure is that at some point, the receptor is "processed" and the estrogen molecule released.
Meanwhile, in the liver, estradiol molecules carried in by the bloodstream are broken down. There are two different chemical routes that estradiol molecules can take here. The first one alters carbon atom number 2 and converts estradiol into a compound called 2-hydroxyestrone. The second pathway alters carbon atom number 16, producing a metabolite called 16-beta-estriol.The proportion of 2 to 16 turns out to be critical. The 16-metabolite is still estrogenic: it can recirculate through a woman's body and bind to estrogen receptors just like its parent, estradiol.
Moreover, 16 is capable of directly damaging the DNA strand.In contrast, the 2-metabolite is minimally estrogenic and is non-toxic to DNA. Clearly, a low 16 to 2 ratio is desirable. Some xenoestrogens act to skew this balance away from 2 and towards the 16 pathway, as we shall see.
The Dawn of Xenomania...
Now enter xenoestrogens.
During World War II, legions of organic chemists were put to work by their governments to solve wartime problems. The pesticide DDT, for example, was perfected and developed as a means to control body lice and, therefore, typhus. Herbicides 2,4-D and 2,4,5-F were developed as chemical defoliants for fighting jungle warfare.These new chemicals were synthetic, meaning they are derived from petroleum and manufactured in a laboratory. Whole new classes of chemicals not found in nature were thus created.
Organochlorines, of which DDT and PCB's are two, are made by attaching chlorine atoms to carbon chains, for example. While chlorine and carbon are common elements of the natural world, they are almost never found bonded together.At the end of the war, the US government helped the petrochemical industry to find private markets for their products. DDT was used for mosquito and agricultural pest control. Chemical defoliants were used in national forests to control shrubs. Lawn, garden and household insecticides were developed. Detergents replaced soaps. Plastics replaced celluloid.
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