Topic 4.11 Effects of endocrine active substances in wildlife species: Genetic, biochemical, and physiological factors in variable susceptibility to endocrine disruptors*

Responses to endocrine active substances (EASs) in animals are various, and differences between the responses among individuals, populations, and species are well known. These differences are observed not only in EASs but in most environmental chemicals including synthetic and naturally occurring ones. The basic differences in sensitivity to EASs are attributed to that of affinity or specificity of the receptors to EASs at the cellular level. Although the nucleotide sequences encoding for estrogen receptor proteins have been documented in several species and the functions of the receptors are the same, the ability to bind the natural hormones and the estrogenic xenobiotics is not necessarily identical. The reproductive endocrine system is basically common among vertebrates, but chemical types of hormones, physiological roles of hormones, and the basal blood levels of hormones differ among each species, especially in sex steroids. These differences cause various types of responses and sensitivity to EASs among animal species. Xenobiotic metabolism is important for the genetical, biochemical, and physiological factors concerning the influence of EASs. Some EASs directly inhibit cytochrome P450 (CYP) activity as was reported in tributyltin that inhibits CYP19 (aromatase) activity causing imposex in neogastropods. Some organochlorines including dioxins stimulate arylhydrocarbon (Ah) receptor-mediated xenobiotic metabolism, and result in the metabolic disruption of steroid hormones such as estrogen as were reported in eggshell thinning in birds of prey and uterus occlusion in seals. CYP activity greatly differs among wildlife species in both terrestrial and aquatic organisms, and these differences are significantly responsible for the multiple effects or toxicity of EASs. Sex and age differences also cause different responses to EASs and are largely due to the differences in xenobiotic metabolizing activities. *Report from a SCOPE/IUPAC project: Implication of Endocrine Active Substances for Human and Wildlife (J. Miyamoto and J. Burger, editors). Other reports are published in this issue, Pure Appl. Chem. 75, 1617–2615 (2003). ‡Corresponding author