There are several questions that need to be addressed such as (1) how does estrogen regulate MAPK related gene expression through IGF-I and the IGF-IR/MAPKp44/42 pathway; (2) what is the role of E2 in the activation of IGF-IR leading to MAPKp44/42 phosphorylation of ERα at the serine 118 site; (3) which specific mediators of the signaling pathways are involved in the interactions of IGF-I/IGF-IR and ERα in uterine leiomyomas. The gene discussed is ESR1; the disease is Uterine leiomyoma.