Integration of genomic and nongenomic estrogen receptor and progesterone receptor signaling pathways. Estrogen receptor (ER) and progesterone receptor (PR) can bind directly to DNA-specific sequences or indirectly by binding to other transcription factors. In addition, ERα and PR are able to activate several signaling pathways (mitogen-activated protein kinases (MAPKs), JAK/STAT, SRC or phosphatidylinositol-3-kinase (PI3K)) (blue arrows). In parallel, epidermal growth factor receptor (EGFR) activation by epidermal growth factor (EGF) or mediated by ERα activates MAPKs, which in turn can phosphorylate and probably activate ERα or PR. Protein kinase A (PKA) and PAK phosphorylate and activate ERα (red arrows). cAMP is involved in the activation of both ERα and PR receptors and can be induced by membrane receptors such as GPR30 or mPR. Besides, coactivators can participate in ERα activation by crosstalk with other signaling pathways; the coactivator coactivator-associated arginine methyltransferase-1 (CARM1) activates ERα by cAMP signaling, leading to ERα phosphorylation. Once phosphorylated, ER and CARM1 interact and can bind to the DNA to regulate target genes. E2, 17β-estradiol; HB, heparin-binding; PG, progesterone.