Figure 1.

Structure and signal transduction of estrogen receptor (ER) and progesterone receptor (PR). (A) Schematic representation of the ER structural regions. Both ERα and ERβ genes are expressed from 8 exons and have five interconnected segments of functional domains. The number of amino acids and percent homology between the two ERs for each segment are indicated (Figure reproduced from [11]). (B) Mechanisms of estrogen receptor signaling pathway. Estrogen (E2) first binds ERs, then ERs dimerize and translocate into the nucleus. These complexes bind to estrogen response elements (EREs) and regulate downstream gene transcription (Figure reproduced from [10]). (C) Schematic overview of estrogen and G-protein coupled estrogen receptor (GPER) interaction and activation in estrogen signaling pathways. The GPER is an alternate ER with seven-transmembrane domains that mediate nongenomic estrogen-related signaling. Membrane estrogen can interact with GPER, which further activates downstream protein-kinase cascades (Figure reproduced from [18]). (D) The structure and activation of PR major isoforms. PR-A is the truncated form lacking the first 164 amino-terminal and is transcriptionally inactive. PR-A also lacks a third transactivation domain (AF3) located in the truncated area, which is known to repress transcriptional activity mediated by PR-B and some other steroids. PR-B binds through its DBD to the progesterone response element (PRE) on the promoter and functions as an activator of the progesterone response gene (Figure reproduced from [24]).