Estrogen agonist and antagonist action on the human estrogen receptor in Drosophila

The estrogen receptor (ER) regulates the expression of genes involved in th e growth, proliferation and differentiation of skeletal, cardiovascular, ne ural and reproductive tissues. A basic scheme for the mechanism for ER acti on has been developed, but precise details on the interactions between ER a nd the cellular signaling and transcription machinery required for receptor -mediated regulation of specific target genes are still lacking. We have de veloped a genetic approach to explore the functional interactions of ER. in this work, we describe the development of an estrogen responsive system in the fruit fly, Drosophila melanogaster. Transgenic flies carrying the huma n ER alpha and an estrogen responsive green fluorescent protein (GFP) repor ter gene were constructed. In vivo expression of the GFP reporter gene was observed when larvae were grown on a food source containing steroidal or no nsteroidal estrogens. The induction of the reporter gene by estrogens was M ocked upon treatment with tamoxifen, an estrogen antagonist. However, we fa iled to recapitulate ligand-independent activation of the receptor in vivo or in cultured Drosophila cells. An estrogen responsive Drosophila system c ould be used to identify and characterize the complex functional interactio ns between ER and the other components of the cellular transcriptional appa ratus.