Estrogen and progesterone are steroid hormones that play a pivotal role in the regulation of mammalian reproduction. One primary action of these hormones is to regulate the development and function of the uterus. These hormones act by regulating the transcription of specific genes in the uterus. The actions of these hormones are mediated by their specific hormone receptors. These receptors are nuclear transcription factors, whose transcriptional regulatory activity is mediated by the binding of the specific steroid to these molecules. Once these receptors bind hormone, they can bind to specific cis-acting sequences in the promoter region of responsive genes and regulate transcription of these genes. In the regulation of transcription, these receptors interact with specific cofactors to activate the transcriptional machinery. A second gene family, the Steroid Receptor Coactivator (SRC) family, has been identified that serves to modulate the transcriptional activity of the hormone receptors. To date, three members of the SRC family have been identified. During the last decade, gene targeting technology has been used to identify the role of these receptors in the regulation of reproduction and uterine biology.