Estrogen receptor mediates anti-inflammatory action in Crohn’s disease
Accumulating evidence highlights the meaningful impact of estrogen receptors in physiology and pathophysiology of the colon.
Crohn’s disease (CD) is one of the inflammatory bowel disease (IBD) types characterized by chronic intestine inflammation. Although intestinal microbiota has been identified as the main factor responsible for immune response alternation in the past decade, other factors involved in CD pathogenesis, such as genetic and environmental, have been described.
Etiology of CD is still poorly understood and treatment of CD patients generally consists of maintaining long-term remission. There are some therapeutic strategies but unfortunately many of them appear to be not effective in all hospitalized CD patients. For instance, it was shown that over a half of CD patients who received corticosteroid therapy did not respond to treatment or needed surgery intervention1.
Consequently, biological therapy such as anti-tumor necrosis factor α (TNFα) or anti-α4-integrin is the most effective approach for CD patients2. Nevertheless, some studies indicate that about 40% of IBD patients have been identified as non-responding to treatment and many of anti-TNFα-treated patients are developing resistance for anti-TNFα monoclonal antibody3.
It has been documented that estrogens can regulate chronic inflammatory diseases such as arthritis, systematic lupus erythematosus, experimental autoimmune encephalomyelitis, thyroiditis, endometriosis and colon inflammation4.
Epidemiological studies indicate that oral contraceptives (OC) and hormone replacement therapy (HRT) in post-menopausal women are related with occurrence and development of IBD. Kane et al. documented that hormone replacement therapy in post-menopausal women with either IBD type, i.e. CD and ulcerative colitis (UC) is related with reduction of disease activity as compared to non-HRT users5. Additionally, decline of IBD activity in post-menopausal women seems to be associated with duration of exogenous hormone supplementation. On the other hand, it was estimated that OC or HRT current users have increased risk of developing CD6.
The effect of estrogens is mediated by interaction of estrogens with cognate receptors and triggering estrogen-dependent signaling pathways. G protein-coupled estrogen receptor (GPER, earlier known as GPR30) is a membrane-bound estrogen receptor responsible for non-genomic action of estrogens.
In contrast to nuclear estrogen receptors, i.e. ERα and ERβ which are liable to direct gene regulation, activation of GPER results in rapid modulation of several proteins, leading to signal transduction and changes at the transcriptional level. GPER is widely distributed in human tissues including intestine where it may act as a potent mediator of the immune response.
Studies of metabolic syndrome in GPER knockout mice revealed higher level of plasma pro-inflammatory cytokines compared to wild type mice7. In line, it has been documented that GPER exerts an anti-inflammatory effect in endothelium and vascular tissue8,9.
Read full report at https://www.nature.com/articles/s41598-019-43233-3