Environmental Estrogens

Environmental Estrogens Estrogen is a powerful, natural hormone produced by females of complex organisms (and in small amounts by males) to suppress ovulation during the menstrual cycle, to suppress androgen formation, and to protect against diseases such as osteoporosis, heart attack and some cancers (such as breast cancer and uterine cancer). (1) In contrast, environmental estrogens are synthetic organic compounds which act like hormonal estrogen, but can affect reproductive health of more complex organisms contributing to sterility, infertility, and higher incidences of cancer. (2) With 50 different chemicals currently identified to exhibit estrogenic activity in complex organisms and with the threat of environmental exposure on the rise, environmental estrogens could be a significant contributor to adverse health affects of humans and complex animals. (3) Chemically, estrogens have an aromatic A-ring, with a C-18 base skeleton absent of a C-17 side chain. The most common, natural estrogen is estradiol which metabolizes in the liver to the less active forms of estrone and estriol. Most natural estrogens are short-lived as they are cycled through the bloodstream; they do not accumulate in fat or surrounding tissue and are easily broken down by the liver. (1) Esterdiol brings about cellular effects by activating genes in target cells. Since esterdiol is soluble in lipids, it can easily pass through the phospholipid bilayer of the cell membrane and nuclear membrane. (4) Naturally, the hormone, esterdiol, binds to an estrogen receptor site within a specific target cell of the human body. An estrogen receptor is a large protein molecule with different regions of articulation that perform certain functions such as: estrogen binding, dimer formation, response element binding, or promoter sequence identification. The esterdiol-receptor complex then binds to another esterdiol-receptor complex to form a dimer which is stabilized by a terminal carboxyl-ligand hydrogen bond. After identification and articulation with a DNA sequence, a promoter sequence is identified, and the specific function of the hormone and target cell is carried out. (5) Environmental estrogens are synthetic estrogenic (estrogen-like) chemicals which are more stable, remain in the body longer, accumulate in fat and surrounding tissue, and can have different influences on the endocrine system. (1) They are commonly found in manufactured products such as: insecticides, herbicides, fungicides, nematocides, (i.e.: atrazine, methoxychlor, DDT & metabolites, kepone), industrial chemicals (i.e.: PCBs, PCPs), heavy metals, household products (i.e.: dioxins, furans) and products associated with plastics (i.e.: bisphenol A). (6) Environmental estrogens have a wide variety of molecular structures, none of which are related to naturally occurring estrogen. Due to the unique molecular structure of the endocrine receptor, this protein is capable to bond with a broad range of molecules. With the use of hydrogen bonding and van der Waals forces, environmental estrogens interact and bind with the estrogen receptor to produce an unnatural response. Initial indications believed that environmental estrogens directly affected, altered, or denatured DNA. (4) Recent studies have shown that environmental hormones do not alter genes. They can impact the endocrine system by: mimicking the effect of the actual hormone, causing an abnormal response or elicit no response, binding with other endocrine receptors to create an alternate reaction which interferes with normal hormone reaction, or altering the production and breakdown or hormone receptors and natural hormones. (1), (2), (7) With these types of interactions, the longer the synthetic estrogen complex articulates with the DNA sequence, the longer the gene activity is affected. (4) Another interesting facet of environmental estrogens is their existence as chiral molecules and as enantiomers. Enantiomers are mirror images of the synthetic compound that also have identical physical properties. Enantiomers are released into the environment in equal ratios within most compounds. Studies have shown that biological activity maybe enantiomer-specific. For example the commercial insecticide DDT is composed of 25% (-)o,p’-DDT and (+)o,p’-DDT. Estrogenic activity in mammals and fish appears to be more active for (-)o,p’-DDT when compared to a racemic mixture of (-)o,p’-DDT and (+)o,p’-DDT. (8) The racemic mixture appears to only have weak estrogen effects on mammals and fish. There have been many documented cases of environmental estrogens affecting wildlife. In 1980, a large amount of DDT was dumped into Lake Apopka, Florida. In the following years scientists observed a sharp decline in the number alligator hatchlings. Some of those young that survived were documented with abnormal reproductive systems varying from decrease in penis length, infertility, or sterility of the developing alligators. Further tests revealed that DDE, a DDT metabolite, was affecting egg and fetus development by elevating or depressing estrogen and androgen levels. The Florida Panther was brought near extinction because reproductive abnormalities in the young were unable to propagate the species. It was identified that raccoon’s, a primary food source of Florida Panthers, had increased levels of DDE. Birds of the Great Lakes that were exposed to PCBs and dioxins have a greater incidence of embryo mortality and deformation. (2) Rhesus monkeys exposed to dioxin have an increase in endometriosis of the developing juvenile. (6) The transfer of environmental estrogens from mother to fetus is one common thread that becomes apparent in each of these cases. Environmental estrogens disrupt the hormone balance of the developing fetus causing minor to severe reproductive abnormalities. (2) It is believed that environmental estrogens can similar impacts on human health. Adult females exposed to environmental estrogens are potentially at risk of giving birth to infants with genital or urinary tract malformations or of undetermined sex. (2) Since 1950, children who were exposed to environmental estrogens experience the onset of puberty at an early age. (6) Exposure to ecoestrogens before or during puberty also appears to increase the risk of developing breast, uterine or testicular cancers. Men exposed to ecoestrogens are at risk of a lower sperm count while females may experience a shorter menstrual cycle or a shorter lactation period after childbirth. (2), (6) Studies have shown an inverse relationship between the amount environmental estrogen and the subsequent affect on the endocrine system. of At low doses, the affect on the endocrine system appears to be significantly greater, whereas higher doses seem to shutdown or slowdown the endocrine system. (2) Unfortunately, current testing methods measure the toxicity based on maximum exposure levels. Environmental estrogens can cause significant hormonal changes at doses 50 times lower than the maximum level of exposure recommended by the American Cancer Society. (3) In 1938, diethylstilbestrol was the first synthetic chemical identified to have estrogenic effects for the benefit of cattle growth hormone. Only a few years later this same chemical was administered to women who were at risk of miscarriages. In 1971, diethylstilbestrol became associated with rare forms of vaginal cancer as well as changes in the female reproductive biology of offspring of women who took this drug. There are many similar chemicals used in many products today that can potentially have adverse health affects to young children, unborn fetuses, or wildlife. Many commercial and industrial chemicals are not tested as rigorously for adverse health effects on humans or wildlife as compared to other foods and medicinal drugs. (4) Environmental estrogens have the potential of becoming a silent, indirect, yet harmful participant in the health of wildlife, humans, and their offspring.