Is synergy of estrogen mimics an illusion?

It's not hard to find evidence of synergy in the endocrine system. Simultaneous exposure to one unit of hormone A and one unit of hormone B often yields effects exceeding--by 2 to 10 times--the sum of effects seen with each hormone alone. Last year, however, a team of researchers in New Orleans reported a startling synergy in which low-level exposures to two estrogen-mimicking pollutants generated as much as 1,600 times the effect seen with just one of the agents.

Now it appears that this amazing synergy (SN: 6/8/96, p. 356) was too bad to be true.

At the fourth federally sponsored Estrogens in the Environment meeting, held last week in Arlington, Va., a spate of studies reported finding no evidence of synergy between estrogen-mimicking pollutants. Two of the studies used the same pesticide duo--dieldrin and toxaphene--that had exhibited the greatest synergy in the New Orleans tests. A third study employed 10 different tests to probe another pesticide pairing studied by the New Orleans group.

John A. McLachlan, head of the Center for Bioenvironmental Research at Tulane and Xavier Universities, where the New Orleans study was conducted, noted at the meeting that even his group couldn't replicate its initial results, though they still find small amounts of synergy. "We've struggled mightily during the last 6 months to find a mechanism to explain our early results," he told Science News. Yet none of these studies substantiated the earlier, dramatic findings.

Consequently, he said, "it seemed only appropriate to withdraw the paper," which he did in the July 25 Science.

With estrogen mimics, "nobody's been able to get synergy. That's the long and the short of it," argues Stephen H. Safe of Texas A&M University in College Station, a coauthor of several studies that have found only additive effects of such agents. Though synergy can be seen between distinct types of hormonelike agents, he says that what made McLachlan's initial report unique was its claim that all the agents were operating through the same estrogen-receptor pathway. "I'll be very surprised if there's synergy ever found for two compounds acting through the same pathway," Safe says.

David P. Crews of the University of Texas at Austin is less certain. He and Judith M. Bergeron recently replicated their earlier study showing a fivefold synergy in the ability of estrogenlike pollutants to alter the gender of developing turtles (SN: 10/8/94, p. 239). Together with McLachlan's team, they have also demonstrated a roughly fourfold synergy between various natural estrogens.

However, Bergeron concedes, "we have not yet confirmed that [any of this synergy] works through a single receptor."

In fact, points out Frederick S. vom Saal of the University of Missouri-Columbia, several studies at last week's meeting show that some estrogen mimics do not work solely through estrogen pathways. "So it might be possible for them to exhibit synergy using two different pathways."