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David P. Crews Ashbel Smith Professor of Zoology and Psychology Section of Integrative Biology University of Texas-Austin

Endocrine Disruptors: Present Issues, Future Problems

Guest Lecture for Fall 1999 Graduate Seminar:   Hormones, Behavior & Endocrine Discrupting Chemicals in the Environment

ABSTRACT: A variety of natural products and synthetic chemicals, known collectively as endocrine-disrupting compounds (EDCs), mimic or interfere with the mechanisms governing vertebrate reproductive development and function. At present, research has focused on the (i) morphological and functional consequences of EDCs, (ii) the identification and determination of relative potencies of synthetic and steroidal compounds having endocrine disrupting effects, (iii) the mechanism of action of EDCs at the molecular level, and (iv) the recognition that in "real life," contamination usually reflects mixtures of EDCs. Future research must address (i) the interactive nature of EDCs and particularly whether the threshold concept as developed in toxicological research applies to xenobiotics, (ii) determine when and how EDCs act at the physiological level, particularly how they may organize the neural substrates of reproductive physiology and behavior, (iii) document species, individual, and even tissue differences in the effects of these compounds, and (iv) examine how adaptations may evolve in natural populations with continued exposure to EDCs. Several predictions are offered that reflect these new horizons. Specifically, (i) The threshold assumption cannot be applied to xenobiotics since they mimic the actions of endogenous molecules (e.g., estrogen) critical to development; hence, the threshold is automatically exceeded with exposure. (ii) Behavior compounds and magnifies the effects of EDCs over successive generations. That is, bioaccumulated EDCs inherited from the mother not only influence the morphological and physiological development of the offspring, but also their reproductive behavior as adults that, in turn, has organizational actions on the sexual development of their own young. (iii) The sensitivity of a species or an individual to a compound is related to species (individual) -typical circulating concentrations of gonadal steroid hormones. Related to this is the likelihood that alternate forms of the putative receptors may be differentially distributed, thereby contributing to the different effects that have been observed. (iv) Except in extraordinary situations, populations often continue to exist in contaminated sites. One possible explanation for this observation that needs to be considered is that animals can rapidly adapt to the nature and levels of contamination in their environment. It is unlikely that successive generations coincidentally become insensitive to gonadal steroid hormones as they are biological regulators fundamental to development and reproduction. Rather, adaptive alterations in the gene(s) encoding steroid receptors may occur with chronic exposure to EDCs that allow the sex hormone receptor to discriminate natural steroids from EDCs.   RELATED READING: Crews, D. 1996. Temperature-dependent sex determination: The interplay of steroid hormones and temperature. Zoological Science 13:1-13. Bergeron, J.M., E. Willingham, C.T. Osborn III, T. Rhen, and D. Crews. 1999. Developmental synergism of steroidal estrogens in sex determination. Environmental Health Perspectives 107:93-97. To request one of Dr. Crew's reprints (since 1993)   ONLINE RESOURCES: Dr. Crew's Departmental Pages Dr. Crew's Lab Pages

OTHER FALL 1999 SPEAKERS:   Theo Colborn   .  Lou Guillette   .  Victor Apanius   .  Fred vom Saal

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