The major goal of this research project is to understand the molecular mechanisms by which steroid and peptide hormones regulate the expression of specific genes in differentiated cells. We will focus our attention on the chick transferrin and ovalbumin genes because these two egg white genes represent well-characterized examples of tissue-specific expression and hormonal regulation. The ovalbumin gene is expressed exclusively in the oviduct in response to estrogen and progesterone; however, tissue culture experiments have recently demonstrated that this steroid response is completely dependent on the additional presence of an insulin-related growth factor (IGF). The transferrin gene is expressed and regulated in at least three differentiated tissues: the oviduct, liver, and testis. Our specific objectives are to (1) study the IGF-mediated events which modulate the response of the ovalbumin gene to estrogen (2) identify the DNA sequences that interact with steroid receptors and regulate transcription of the transferrin and ovalbumin genes (3) explore the mechanisms which lead to gene commitment and tissue-specific expression of the transferrin gene. Our approach will utilize hormone-responsive oviduct cells in culture as an in vivo assay system for regulatory proteins and DNA sequences that can be introduced into the living cells by microinjection. The tissue-specific expression of the transferrin gene will be examined by introducing the chick transferrin gene into the mouse genome via oocyte microinjection. The expression and regulation of the chick gene in differentiated mouse tissues will then be examined. We expect these studies to further elucidate the basic mechanisms by which reproductive hormones control the developmental program of growth, differentiation, and specific gene expression in target tissues.
