Significance of G Protein-Coupled Estrogen Receptor in the Pathophysiology of Irritable Bowel Syndrome, Inflammatory Bowel Diseases and Colorectal Cancer
Damian Jacenik, Wanda M. Krajewska
Abstract
The regulatory role of estrogens and nuclear estrogen receptors, i. e., estrogen receptor α and β has been reported in gastrointestinal diseases. However, the contribution of G protein-coupled estrogen receptor, the membrane-bound estrogen receptor, is still poorly understood. Unlike nuclear estrogen receptors, which are responsible for the genomic activity of estrogens, the G protein-coupled estrogen receptor affects the "rapid" non-genomic activity of estrogens, leading to modulation of many signaling pathways and ultimately changing gene expression. Recently, the crucial role of G protein-coupled estrogen receptor in intestinal pathogenesis has been documented. It has been shown that the G protein-coupled estrogen receptor can modulate the progression of irritable bowel syndrome, inflammatory bowel diseases such as Crohn's disease and ulcerative colitis as well as colorectal cancer. The G protein-coupled estrogen receptor appears to be a potent factor regulating abdominal sensitivity and pain, intestinal peristalsis, colitis development, proliferation and migration potential of colorectal cancer cells and seems to be a useful target in gastrointestinal diseases. In this review, we present the current state of knowledge about the contribution of the G protein-coupled estrogen receptor to irritable bowel syndrome, inflammatory bowel diseases and colorectal cancer.