Effects of Environmental Endocrine Disruptors and Phytoestrogens on the Kisspeptin System - Kisspeptin Signaling in Reproductive Biology - page 446

To date, the EPA has identifi ed hundreds of compounds that meet this defi nition and
thousands of others are suspected of having similar properties (for more information visit
http://www.epa.gov/endocrine/Project.html ) [ 14 , 15 ]. These compounds are contained in
a wide array of consumer products, including cosmetics and other personal care items,
pesticides, plastics, building materials, food containers, medical equipment, epoxy resins,
paper products, furniture, electronics, and as “inert” ingredients in pharmaceuticals. They
also contaminate our air, water, food supply, and bodies, including those of the unborn
[ 16 ]. Not all EDCs are anthropogenic, however. Numerous plant-derived compounds,
most notably the phytoestrogens, also meet the defi ning criteria of an EDC. Understanding
how these naturally occurring compounds impact neuroendocrine systems, such as the
kisspeptin system, will help elucidate the evolved mechanisms by which organisms are
sensitive to synthetic compounds with similar structural and chemical properties. Growing
awareness of how ubiquitous EDC exposure has become has generated substantial, and
growing, public concern regarding the potential long-term risks they pose for wildlife and
human health. Systematic evaluation of this risk requires uncovering the mechanisms by
which these compounds act within our bodies to confer disease.
Endocrine Disruption or Environmental Sensing?
The idea that environmental chemicals can interact with mammalian physiology is not
a radical notion. All living things evolved in a soup of chemicals, and interspecies
chemical warfare is a defi ning element, if not a critical driver, of evolutionary history.
For example, plants and animals generate potent neurotoxins, such as venoms and
poisons, to protect against predation or enhance their own deadly prowess. Cytochrome
P450 enzymes (CYP), required for steroid hormone synthesis, appear to have evolved
as a defense against botanical poisons and then repurposed [ 17 ]. Moreover, plant alka-
loids have historically been, and continue to be, our single greatest source of medici-
nal therapeutics. Some of the most well known are caffeine, cocaine, nicotine,
strychnine, morphine, quinine, and mescaline, a powerful hallucinogen. Plant-derived
compounds can also be endocrine disrupting [ 18 ]. Phytoestrogens have proven to be
an important environmental cue and endocrine-active compound for numerous spe-
cies, including rodents [ 19 ], birds [ 20 ], cheetahs [ 21 ], and grazers like cattle and sheep
and the southern white rhinoceros [ 22 - 25 ]. There are several classes of phytoestro-
gens, all of which structurally resemble mammalian estrogens. Like bisphenol
A (BPA) and other synthetic EDCs, phytoestrogens have historically been thought to
act primarily through estrogen receptors [ 26 ], but they are also tyrosine-kinase inhibi-
tors [ 27 , 28 ] and modulate DNA methylation and chromatin confi guration [ 29 ].
Genistein (GEN) is a member of the most well-known class, the isofl avones, which are
most abundant in soybeans and soy-based foods. Others, such as the coumestans, are
prevalent in alfalfa, clover, and other pasture legumes, including the ones sheep and
other herbivores typically graze on. Phytoestrogens play an important role in plant
defense [ 30 ], including the recruitment of nitrogen-fi xing bacteria [ 31 ] and conferring
resistance to fungi [ 32 ]. Thus plants produce them when under stress including disease,