Glucose conjugation is the major metabolic process leading to the inactivation and elimination of testosterone in this species. Metabolism of testosterone by the mud snail was investigated during the past year. Surprisingly, no significant conversion of testosterone to polar hydroxylated or conjugated derivatives by the mud snail was detected. Rather, testosterone was rapidly converted to highly apolar derivatives that are sequestered within the organism. The identification of these testosterone derivatives is underway.
Preliminary indications are that they are fatty acid conjugates of testosterone.
The discovery that testosterone is not significantly eliminated from the mud snail as polar conjugates indicates that interference with such processes by the chemicals under study, as originally hypothesized, is unlikely. Once the testosterone derivatives have been identified, experiments will be undertaken to determine whether the chemicals under study either interfere with the formation of the nonpolar derivatives or facilitate the de-conjugation of the derivatives. Either process would increase the amount of free testosterone in the snails that could be responsible for putative masculinizing effects of the chemicals. The second objective of the program is to identify physiological perturbations associated with metabolic androgenization. Using the crustacean model, we have determined that chemicals that elicit metabolic androgenization also interfere with normal embryo development.