on the relative impacts of phytoestrogens and synthetic hormone disruptors.
RR, EP Banks, B Bullock, and WN Jefferson 2001. Uterine adenocarcinoma
in mice treated neonatally with genistein. Cancer
Research 61: 4325-4328.
et al. report that when neonatal mice are exposed to genisteina
phytoestrogen present in soylater in life they develop uterine
cancer of the same form caused by diethylstilbestrol
(DES). The levels of genistein used in these experiments are comparable
to those found in infant formula based on soy. More...
H, M Tabata, S Onodera and K Takeda. 1999. Passage of bisphenol
A into the fetus of the pregnant rat. Journal of Health Science
administered bisphenol A (10 ppm) appears immediately in materal
blood and is transferred into the fetus. The concentration of BPA
in the fetus peaked within one hour after administration, reaching
11 ppb. in fetal blood.
paper suggests that BPA passes easily through the placental barrier,
bypassing protections that limit the impact of native estradiol
SF, MK Robinson, A Notides, LJ Guillete, Jr. and JA McLachlan. 1996.
A yeast estrogen screen for examining the relative exposures of cells
to natural and xenoestrogens. . Environmental Health Perspectives
forbidding title of this article may make one of its key results less
than obvious. Arnold et al. show that certain xenoestrogens
(a catch-all term for synthetic contaminants like DES, DDT, etc. which
interfere with estrogen signalling) are less likely to be bound by
blood serum than estrogens found naturally in the body. This is important
because it sheds light on why apparently "weakly" estrogenic contaminants
may nonetheless have important effects. The term "weakly estrogenic"
comes from comparing the tightness with which the contaminant binds
with the estrogen receptor. Natural estrogens bind very tightly. Contaminants
less so, sometimes less by a factor of 1000x or more. This might be
taken to indicate that they represent little risk.
this paper points out is that binding affinity is only one of a
series of factors that control risk. Blood serum contains binding
proteins which, in effect, reduce the amount of natural estrogen
that is freely available to enter cells and interact with estrogen
receptors. Arnold et al.'s work shows that these blood serum
proteins remove much more of the natural estrogen than of the contaminants.
As they put it: "As shown in this study, the bioavailability of
xenoestrogens in serum is apparently greater than that of estradiol"
(one form of natural estrogen).
SF, BM Collins, MK Robinson, LJ Guillette, Jr and JA McLachlan. 1996.
Differential Interaction of Natural and Synthetic Estrogens with
Extracellular Binding Proteins in a Yeast Estrogen Screen Steroids
et al. used the yeast estrogen screen technique to evaluate
interactions between extracellular binding proteins and ovarian estrogen,
phytoestrogen and xenobiotic estrogens. The experiments involved yeast
cells genetically engineered to indicate estrogen receptor activity
when incubated in the presence of an estrogen. They report that the
activities of human estradiol and two phytoestrogen--coumestrol and
genestein--are reduced in the presence of three extracellular binding
proteins found in human serum. The activities of three xenobiotic
estrogens--DES, kepone and p,p'-DDT were only minimally reduced.
research team thus found that the blood proteins do provide protection
from the plant estrogens they tested but do not appear to protect
against the man-made estrogens that were used in the experiment.
Commenting on these specific results, the team noted that "phytoestrogens
bind... with a higher affinity than synthetic estrogens suggesting
that humans have evolved a mechanism to protect themselves from
continuous exposure to phytoestrogens. On the other hand, the relative
inability of synthetic estrogens to bind indicates a potential fundamental
difference in the interaction of estrogens from diverse sources
with these proteins."
J, J Larsen, P Christiansen, A Giwercman, P Grandjean, LJ Guillette
Jr., B Jegou, TK Jensen, P Jouannet, N Keiding, H Leffers, JA McLachlan,
O Meyer, J Muller, E Rajpert-De Meyts, T Scheike, R Sharpe, J Sumpter,
and NE Skakkebaek. 1996. Male Reproductive Health and Environmental
Xenoestrogens. Environmental Health Perspectives 104(Suppl 4):741-803.
paper is the result of a one-week workshop convened at the request
of the Danish Environmental Protection Agency in Copenhagen in January
1995. Toppari et al. review the literature on changes in male
reproductive health, on chemicals known to have estrogenic activity
and on sources of human exposure.
phytoestrogens, they comment: "Large amounts of phytoestrogens such
as isoflavones can be ingested daily by humans, especially in a
vegetarian diet. Antiestrogenic action of isoflavones was demonstrated
in women who consumed a soy protein-enriched diet containing 45
mg isoflavones daily for 1 month....
A study of postmenopausal women in Australia suggested an estrogenic
influence by phytoestrogens on the vaginal epithelium.
Many infants are fed with soy-based milk-substitute formulas rich
in phytoestrogens. There are no data available about the possible
endocrine effects in children, but it is presumed that the situation
would be radically different from the adult because of the negligible
endogenous production of estrogens in infancy (especially in male
infants). Female rats exposed neonatally to phytoestrogens show
an increased incidence of premature anovulatory syndrome in adult
life. This syndrome is recognized as a classical consequence of
inappropriate exposure to estrogens in neonatal life. Many phytoestrogens,
such as lignans and isoflavonoids, are metabolized and excreted
in urine similarly to endogenous estrogens. Thus, they may not bioaccumulate
in the body."
SC, FS vom Saal, KA Thayer, MG Dhar, M Boechler and WV Welshons.
1997. Relative binding affinity-serum modified access (RBA-SMA)
assay predicts in vivo bioactivity of the xenoestrogens Bisphenol
A and Octylphenol. Environmental Health Perspectives 105:70-76.
way to gauge the power of an endocrine disruptor is to carry out
experiments in vitro that reveal the strength with which
the compound binds to a hormone receptor. These studies, while useful
to identify endocrine disruptors whose impacts are a result of direct
interaction with the receptor (not all are), can be misleading because
"binding affinity" is only one parameter of many that
effects a contaminant's potency.
this paper Nagel et al. combine several different types of information
to predict the potency of bisphenol A and octylphenol. Bisphenol
A turns out to be more powerful than predicted simply on the basis
of binding affinity alone, while octylphenol is less powerful. Studies
like this are important in understanding why simplistic
arguments about the quantity of phytoestrogens in the diet are
paper presents new data on the low level effects of bisphenol A,
demonstrating that fetal exposure to environmentally-relevant doses
of bisphenol A (parts per billion, in the range currently consumed
by people), alters reproductive development in mice. More...