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Endocrine disruptor synnergy article withdrawn...
npr syndicated _living on earth_ this sunday did some supurb
journalism--detailed, independent--on this and other e.d. mechanistic
questions. also, dr's vom saal & guillette gave excelent presentations on
the same to a panel at the ncamp conference in march, which video i have
_loe_ mentioned this letter and overviewed the situation (5 attempts at
replication) w/ statements from dr. maclachlan. but they also had dr
desoto saying her lab had gotten 10 fold synnergistic results, and
mentioned that other studies had shown greater than additive effects, tho
not as large as 400-1600 fold. mechanisticly, there is evidence of
multiple sites on the estrogen receptor to accomodate different shapped
molecules, thus corroborating repeated observations of some synnergy.
_loe_ moved on to vom saal's work, which i had heard him present on the
video of ncamp (apparantly published in _proceed. n.a.s._ -- anyone know
the cite?) in which 1/10th of a trillionth gram/ml blood (that approximates
0.1 ppt, right?) of potent estradiol caused significant enlargement of
prostate in mice, but larger doses, around 2 & 5 ppt, i think), caused
shrinkage [von saal used a wonderful anology to receptor binding of ships
not being able to unload their cargo (ie become biologically active) until
they've docked in their port]. as von saal & _loe_ pointed out, this is of
tremendous significance to risk management. guillette at ncamp said
endocronologists have known of this shutting down of the endocrine system
at higher doses for decades. as vom saal said, it may mean the
invalidation of hundreds of tests for endocrine activity. imo, we need to
hit agencies, e.g. epa, over the head with this until they bleed.
>Date: Sat, 2 Aug 1997 18:22:35 -0400
>Subject: Endocrine disruptor article withdrawn...
>Synergistic Effect of Environmental Estrogens: Report Withdrawn
>I write to formally withdraw the report "Synergistic activation of
>estrogen receptor with combinations of environmental chemicals" (7
>June 1996,Ýp. 1489) (1), for which I was corresponding author.
>We have conducted experiments duplicating the conditions of our
>earlier work, but have not been able to replicate our initial
>Also, since our publication in Science (1), others have been unable
>to reproduce the results we reported (2). Meanwhile, people in many
>walks of life have, on their own, put great weight on this report
>as the basis for much discussion, thought, and even public policy.
>Whatever merit this publication contained, and despite the
>enthusiasm it generated, it is clear that any conclusions drawn
>from this paper must be suspended until such time, if ever, the
>data can be substantiated.
>In our laboratory, for the last 6Ýmonths, we have conducted
>experiments to elucidate the mechanisms to explain the phenomenon
>of synergy between estrogenic chemicals. These studies have been
>directed toward understanding the roles that estrogen receptor
>levels (3), the difference between monomer and dimer conditions of
>the estrogen receptor (4), and chemical transport across the cell
>membrane (5) play in the action of weak estrogens. None have
>provided a satisfactory mechanism to explain our earlier findings.
>Taken together, it seems evident that there must have been a
>fundamental flaw in the design of our original experiment. As a
>consequence of our efforts and those of others, and considering the
>impact our report has had in so many quarters, we have decided to
>formally withdraw the paper and its finding. We take this step in
>recognition of the reliance so many have placed on our work.
>Our laboratory will continue to aggressively conduct research on
>environmental endocrinology. We believe there are important and
>verifiable discoveries to be made.
>The co-authors have concurred in writing with this decision.
>John A. McLachlan
>Tulane-Xavier Center for
>Tulane University,1430 Tulane Avenue,
>New Orleans, LA 70112,ÝUSA
>1.S. F.ÝArnold, D.ÝM.ÝKlotz, B.ÝM.ÝCollins, P.ÝM.ÝVonier,
>L.ÝJ.ÝGuillette Jr., J.ÝA.ÝMcLachlan, Science 272Ý1489Ý(1996). 2.K.
>Ramamoorthy, et al., ibid. 275, 405 (1997). 3.D. Q.ÝTran et al.,
>Steroids, in press. 4.S. F.ÝArnold et al., in preparation;
>P.ÝM.ÝVonier, J.ÝA.ÝMcLachlan, in preparation. 5.S. F.ÝArnold et
>al., in preparation; D. Q. Tran , et al., Biochem. Biophys. Res.
>Comm. 235, 669 (1997) .
>Volume 277, Number 5325, Issue of 25 July 1997, pp. 459-463.
>©1997 by The American Association for the Advancement of Science.