Lessons Learned In environmental endocrine science, we have made a series of observations that, at first, seemed unconnected. However, now, as the observations start to establish a pattern, we can begin to discern the linkages between them. In the last 20 yr we have discovered the intrinsic biological signaling properties of numerous synthetic environmental chemicals. We are also beginning to learn about the complex network of signaling molecules that facilitate information flow in the communication system of ecological life. In the same time period, cell and molecular biology has elucidated many of the signaling molecules necessary for intra- and intercellular communications. The similarities between the signaling strategies adopted by the internal and external world are probably more than coincidental if the evolution of the signaling systems followed, in any way, the convergent pathways suggested in this review.

Environmental signals are chemical messenger molecules functioning in a communication network linking numerous species. One may speculate that the functional aspects of this more globally distributed network might have provided a framework or blueprint to build the internal communication networks of animals, which we call their endocrine systems. As such, similarities in response to such signals in some cases should not be unexpected. Indeed, a central strategy for all life forms is the transmission of important characteristics to their offspring. This also is a form of information transfer in which the signal is embedded in the physical entity being transmitted. Thus, the transmission of genetic information and the utilization of signaling molecules and pathways are intrinsic to life from bacteria to humans. As de Loof (217) states, “communication is the one essential property for life.” Chemicals that alter either or both levels of information flow can have consequences that may be deleterious to the individual or population.

From the study of embryos and evolution the following three patterns emerge:

1. The structural diversity of environmental hormones may reflect the evolutionary background of these chemicals as plant signaling molecules or differentiation specific signals for organisms that do not require an endocrine system. Moreover, signals developed for one communication system may be functionally misinterpreted by another system.

2. Evolutionarily important signals are likely to be those related to reproduction or differentiation of the species and its cells. This information is most crucial to the survival of that species and, likely conserved as pathways, most often misinterpreted. Chemicals synthesized to disrupt the reproductive capacity of insect pests stand a good chance of affecting cell differentiation in unintended species and in unintended ways.

3. Molecules with high informational content can induce long-term changes in a communication system if the information is disseminated at inappropriate times. Hormones that may alter the processing of information by imprinting a response pathway or imparting memory functions in a cell can be expected to have long-term effects on developing organisms. The effect will be related to the number and types of programming mistakes induced.

The patterns underlying evolution and embryogenesis are being uncovered through systematic inquiry using the techniques of molecular and cell biology. As patterns begin to emerge in environmental endocrine science, recognition of similarities to those associated with evolution and development should provide insights to mechanisms and outcomes. Without pattern recognition, there is not the ability to predict, and without prediction there is not the possibility to prevent. If male fruit bats are lactating in Malaysia (218), look for the environmental hormone. If there is a dramatic increase in the cases of premature breast development in Puerto Rico (219), look for the environmental hormone. And, if a 50-yr-old mortician presents with gynecomastia and hypogonadotrophic-hypogonadism with no estrogenproducing tumor (93), look for the environmental hormone.

It has not always been recognized as such, nor has it been applied to environmental endocrine science, but making public health predictions based on environmental chemical confusion or environmental signal misinterpretation has a long and mostly successful history in environmental health sciences and toxicology. One informative example will suffice. From the Middle Ages until as recently as 1959, an acute behavior disorder could result from eating moldy rye bread; the fungal product associated with this condition is a neuroactive compound in humans called ergot and the condition is known as ergotism (220). In the Middle Ages and later, ergotism was known as St. Anthony’s fire since humans consuming infested rye flour behaved as if they were on fire and were thought to be possessed by the devil. This level of knowledge was consistent with the unpleasant consequences usually visited on such individuals. As the association between mold in bread and disease in humans was made, the scientific explanation, the human body’s misreading of the fungal signal, provided a course of public health action— prevent mold from developing in rye flour or if it does, don’t make bread from it.

As the principles underlying environmental endocrine science are developed or discovered, the opportunity to apply them to understand and anticipate the environmental component of human reproductive diseases and developmental disorders should excite endocrinologists. From an environmental stewardship perspective, the evolving concept of environmental signals can provide insights with which to address the impact of hormonally active chemicals on humans and the ecosystems that they share with other species. Disruption of this apparently broad communication system has the potential for global change that transcends the endocrine system.