Comparative Aspects of Estrogen Functions and Measurements in Oviparous and Viviparous Vertebrates

Concern for both humans and wildlife has prompted regulatory agencies to search for methods to screen chemicals for disruption of regulation and responses to estrogen and other reproductive hormones. It is not clear whether tests suitable for hazard assessment in mammals also apply to oviparous (egg-laying) animals, or vice versa. Although estrogenic structures are similar across species, estrogen receptor (ER) differences affecting binding affinity and gene activation do occur. The primary function of estrogen in all species is control of ovulation; secondary functions are gender determination, development of secondary sex characteristics, regulation of mating and breeding behaviors, and regulation of calcium and water homeostasis. Major differences between mammals and egg-layers are production of the egg yolk protein vitellogenin by rrthe liver of oviparous species and eggshell formation. Methods for measuring estrogenic activity include production of gene products, cell proliferation assays, tissue responses, vitellogenin induction, hormone assays, egg production and fertility studies, and development of secondary sex characteristics. General cellular/subcellular tests are proposed for initial chemical screening; those that show estrogenic effects would be tested further using species-specific in vitro assays (e.g., relative binding affinity to the ER). Only those chemicals that elicit effects in this second tier, might need to be tested in a higher tier of whole organism studies.