Endocrine disruptors: Present issues, future directions

A variety of natural products and synthetic chemicals, known collectively a s endocrine-disrupting compounds (EDCs), mimic or interfere with the mechan isms that govern vertebrate reproductive development and function. At prese nt, research has focused on (i) the morphological and functional consequenc es of EDGs; (ii) identifying and determining the relative potencies of synt hetic and steroidal compounds that have endocrine-disrupting effects; (iii) the mechanism of action of EDCs at the molecular level; and (iv) the recog nition that in "real life," contamination usually, effects mixtures of EDCs . Future research must examine (i) the interactive nature of EDCs, particul arly whether the threshold concept as developed in traditional toxicologica l research applies to these chemicals: (ii) when and how EDCs act at the ph ysiological level, particularly how they may organise the neural substrates of reproductive physiology and behavior (iii) the various effects these co mpounds have on different species, individuals, and even tissues; and (iv) how adaptations may evolve in natural populations with continued exposure t o EDCs. Several predictions are offered that reflect these new perspectives . Specifically, (i) the threshold assumption will be found not to apply to EDCs because they mimic the actions of endogenous molecules (e.g., estrogen ) critical to development; hence, the threshold is automatically exceeded w ith exposure. (ii) Behavior can compound and magnify the effects of EDCs ov er successive generations; that is, bioaccumulated EDCs inherited from the mother not only influence the morphological and physiological development o f the offspring but also the offsprings' reproductive behavior us adults. T his adult behavior in twin, can have further consequences on the sexual dev elopment of their own young. (iii) The sensitivity of a species or an indiv idual to a compound is related to species (individual)-typical concentratio ns of circulating gonadal steroid hormones. Related to this is the recent f inding that alternate forms of the putative receptors are differentially di stributed thereby contributing to the different effects that have been obse rved. (iv) Except in extraordinary situations, populations often continue t o exist in contaminated sites. One possible explanation for this observatio n that needs to be considered is that animals can rapidly adapt to the natu re and level of contamination in their environment. It is unlikely that suc cessive generations coincidentally become insensitive to gonadal steroid ho rmones fundamentally important as biological regulators of development and reproduction. Rather, adaptive alterations in the genes that encode steroid receptors may occur with chronic exposure to EDCs, allowing the sex hormon e receptor to discriminate natural steroids from EDCs.