Peter M. Vonier

Synergistic Activation of Estrogen Receptor with Combinations of Environmental Chemicals

Certain chemicals in the environment are estrogenic. The low potencies of these compounds, when studied singly, suggest that they may have little effect on biological systems. The estrogenic potencies of combinations of such chemicals were screened in a simple yeast estrogen system (YES) containing human estrogen receptor (hER). Combinations of two weak environmental estrogens, such as dieldrin, endosulfan, or toxaphene, were 1000 times as potent in hER-mediated transactivation as any chemical alone. Hydroxylated polychlorinated biphenyls shown previously to synergistically alter sexual development in turtles also synergized in the YES. The synergistic interaction of chemical mixtures with the estrogen receptor may have profound environmental implications. These results may represent a previously uncharacterized level of regulation of estrogen-associated responses.

Environmental signaling: a biological context for endocrine disruption.

Endogenous and exogenous chemical signals have evolved as a means for organisms to respond to physical or biological stimuli in the environment. Sensitivity to these signals can make organisms vulnerable to inadvertent signals from xenobiotics. In this review we discuss how various chemicals can interact with steroid-like signaling pathways, especially estrogen. Numerous compounds have estrogenic activity, including steroids, phytoestrogens, and synthetic chemicals. We compare bioavailability, metabolism, interaction with receptors, and interaction with cell-signaling pathways among these three structurally diverse groups in order to understand how these chemicals influence physiological responses. Based on their mechanisms of action, chemical steroid mimics could plausibly be associated with recent adverse health trends in humans and animals.

Affinity of the alligator estrogen receptor for serum pesticide contaminants

Top predators, like the American alligator (Alligator mississippiensis) bioaccumulate and biomagnify persistent pollutants, such as organochlorine pesticides. In a recently published study, several pesticides and pesticide metabolites not previously reported in alligator eggs were identified in the serum of juvenile alligators. This study examines the affinity of these compounds for the alligator estrogen receptor (aER) purified from adult oviductal tissue. Of the 11 compounds studied, 9 showed an affinity for the receptor, causing greater than 50% displacement of estradiol-17 beta from the aER. The most effective compounds were heptachlor epoxide and heptachlor, with IC50 of 19.4 and 26.7 microM, respectively. Two compounds, aldrin and Mirex showed little affinity for the aER. These data suggest that additional compounds are capable of acting as aER agonists or antagonists, but future research is needed to confirm in vivo actions, if any.