Our laboratory currently focuses on endocrine toxicology and particularly “endocrine disruptors”, chemicals that may imitate, inhibit or otherwise modulate hormones and the endocrine system. For many years we have investigated the actions of agricultural herbicides, particularly the mechanisms by which these chemicals disrupt estrous cycling in rodent models used for toxicology screens. We are also using our experience with steroid receptors to uncover details of competitive binding properties of environmentally sensitive chemicals with the estrogen receptor, particularly varying strategies that chemicals use to associate with receptor binding.
Chlorotriazine Herbicides Chlorotriazines, principally atrazine, are a class of herbicides used widely in the agriculture industry. In partnership with a principal manufacturer we investigated mechanisms underlying the premature appearance of mammary tumors in female rats during long-term exposure. We initially determined that the herbicides are not estrogenic (a property that would directly stimulate tumor growth). We then noted irregularities of estrous cycling patterns in treated female rats and determined that atrazine administration diminished pituitary LH surges necessary for regular, cyclic ovulation. Failure to ovulate could lead to an elevated estrogen environment and promotion of mammary tumor growth. Investigations continue on mechanisms underlying this neuroendocrine action of chlorotriazines. Xenoestrogen Receptor Binding It is suspected that many hormonally active chemicals contaminate the environment. One group of particular concern are substances that can imitate or inhibit estrogen action. Estrogens principally act on cells via specific receptor proteins, so one way to identify putative estrogen agonists or antagonists is to assess their ability to bind to estrogen receptors in vitro. With support from the US Environmental Protection Agency, we have been investigating binding properties of a number of chemicals identified on the basis of structure.
Eldridge JC, Stevens JT. Preface. In: Eldridge JC, Stevens JT, eds. Endocrine toxicology. 3rd ed. New York: Informa Healthcare; 2010: vii-viii. Eldridge JC, Laws SC. The U.S. EPA's tier 1 screening battery for endocrine disruptor compounds. In: Eldridge JC, Stevens JT, eds. Endocrine toxicology. 3rd ed. New York: Informa Healthcare; 2010: 1-26. Jones NL, Peiffer AM, Lambros A, Eldridge JC. Problem-based learning for professionalism and scientific integrity training of biomedical graduate students: process evaluation. J Med Ethics. 2010; 36(10):620-626. Breckenridge CB, Eldridge JC, Stevens JT, Simpkins JW. Symmetrical triazine herbicides: a review of regulatory toxicity endpoints. In: Krieger RI, Hayes WJ, eds. Hayes' handbook of pesticide toxicology, vol 2. 3rd ed. Boston: Elsevier/Academic Press; 2010: 1711-1723. Eldridge JC, Stevens JT, eds. . In: Endocrine toxicology. 3rd ed. New York: Informa Healthcare; 2010. Jones NL, Peiffer AM, Lambros A, Guthold M, Johnson AD, Tytell M, Ronca AE, Eldridge JC. Developing a problem-based learning (PBL) curriculum for professionalism and scientific integrity training for biomedical graduate students. J Med Ethics. 2010; 36(10):614-619. Peiffer AM, Tytell M, Eldridge JC, Jones NL. Scientific integrity and professionalism instruction using problem-based learning [abstract]. Soc Neurosci Abstr. 2008; 2008(Neuroscience Meeting Planner). Eldridge JC, Stevens JT, Breckenridge CB. Atrazine interaction with estrogen expression systems. Rev Environ Contam Toxicol. 2008; 196():147-160. Laws SC, Yavanhxay S, Cooper RL, Eldridge JC. Nature of the binding interaction for 50 structurally diverse chemicals with rat estrogen receptors. Toxicol Sci. 2006; 94(1):46-56.