The observations that: (1) IGF-IR is required for the interaction and the differential expression of MAPK pathway-related genes mediated by E2; (2) IGF-I gene expression is responsive to E2; (3) the activation of alternative pathways induced by E2 when IGF-IR is silenced enhances our understanding of IGF-I/IGF-IR and E2/ERα interactions and may suggest a multipronged or cocktail approach to fibroid treatment. The gene discussed is IGF1R; the disease is leiomyoma.