SYNERGISTIC RESPONSES OF STEROIDAL ESTROGENS IN-VITRO (YEAST) AND IN-VIVO (TURTLES)

Many environmental agents exert estrogenic activity, Previous studies from our laboratories demonstrated that certain combinations of enviro nmental estrogens (i) reverse the sex of male turtle embryos in a syne rgistic manner (Bergeron et al., (1994) Environ. Hlth Perspect. 102, 7 80-782), and (ii) synergistically transactivate the human estrogen rec eptor (hER) in yeast and mammalian cells (Arnold et al., (1996) Scienc e 272, 1489-1492). Because our findings with synthetic estrogens sugge sted that combinations of naturally-occurring steroidal estrogens migh t also produce synergistic activity of the ER, we used the same model systems to measure the activity of combinations of steroidal estrogens , The activity of combinations of estrone, estradiol-17 beta or estrad iol-17 alpha in yeast strains expressing hER was synergistic at submax imal concentrations of both estrogenic compounds, However, synergy was not observed with mixtures of estrogens when the concentration of one of the estrogens alone was maximally active in yeast, Ligand-binding assays in yeast performed with various radiolabeled estrogens suggeste d that multiple estrogens may interact with the receptor, The estrogen -dependent process of sex-reversal of turtle embryos incubated at a ma le-producing temperature was used to determine whether steroidal estro gens also had synergistic activity in vice, In this instance, a combin ation of estriol and estradiol-17 beta was effective in reversing the gonadal sex of turtle embryos from males to females in a synergistic m anner, Our results suggest that the synergy of some combinations of es trogens, synthetic or steroidal, may play a role in the estrogen-depen dent process of sexual development in certain species. (C) 1997 Academ ic Press.