Crews Laboratory: Focus of Research

4. Endocrine disruption (NSF IBN-9723617)

My fourth research interest relates to the application of basic research to real life concerns. A particularly powerful example is in the area of endocrine disruptors. There is now abundant and undisputed evidence that a variety of natural and man-made chemicals can mimic or antagonize the actions of natural endogenous steroid hormones. Agents such as polychlorinated biphenyls (PCBs), various fertilizers, detergents, and plasticizers acting in minute dosages during embryogenesis result in impaired reproductive performance or even sterility in adulthood. The fact that sex determination in the red-eared slider turtles involves estrogens provides a sensitive bioassay for environmental quality, and we have developed this animal model system as a biomarker of potential contamination by environmental estrogens. Five discoveries that have had a major impact in endocrinology, and particularly relevant to the issue of endocrine disruptors and reproductive development, were made first on the red-eared slider turtle. (i) Alternative form of estrogen receptor mRNA lacking exon four (177); (ii) Synergistic actions of hydroxylated PCBs resulting in reproductive dysfunction (190); (iii) Synergistic actions of steroidal estrogens in estrogen-mediated events (242); (iv) Evidence that the concept of a threshold dosage does not apply for estrogen-mediated endocrine disruptors (243); (v) that mixtures of compounds in ecologically relevant concentrations have different effects than in single compound exposures. This work has been extended to the study of the behavior of mixtures of endocrine disruptors on sex determination (244) as well as long-term effects on reproductive physiology (261).

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	From the Office of Dr. David Crews Focus of Research Note: (numbers in parentheses indicate publication number)
	4. Endocrine disruption (NSF IBN-9723617) My fourth research interest relates to the application of basic research to real life concerns. A particularly powerful example is in the area of endocrine disruptors. There is now abundant and undisputed evidence that a variety of natural and man-made chemicals can mimic or antagonize the actions of natural endogenous steroid hormones. Agents such as polychlorinated biphenyls (PCBs), various fertilizers, detergents, and plasticizers acting in minute dosages during embryogenesis result in impaired reproductive performance or even sterility in adulthood. The fact that sex determination in the red-eared slider turtles involves estrogens provides a sensitive bioassay for environmental quality, and we have developed this animal model system as a biomarker of potential contamination by environmental estrogens. Five discoveries that have had a major impact in endocrinology, and particularly relevant to the issue of endocrine disruptors and reproductive development, were made first on the red-eared slider turtle. (i) Alternative form of estrogen receptor mRNA lacking exon four (177); (ii) Synergistic actions of hydroxylated PCBs resulting in reproductive dysfunction (190); (iii) Synergistic actions of steroidal estrogens in estrogen-mediated events (242); (iv) Evidence that the concept of a threshold dosage does not apply for estrogen-mediated endocrine disruptors (243); (v) that mixtures of compounds in ecologically relevant concentrations have different effects than in single compound exposures. This work has been extended to the study of the behavior of mixtures of endocrine disruptors on sex determination (244) as well as long-term effects on reproductive physiology (261). (Back to Focus Main)