Estrogen decreases tight junction protein ZO-1 expression in human primary gut tissues

Abstract

Females have a higher prevalence of most autoimmune diseases; however, the mechanism is unknown. In this study, we examined the expression of tight junction protein zonula occludens 1 (ZO-1) and estrogen receptor (ER)-α/β in human primary gut tissues by immunohistochemistry, immunofluorescence and qPCR. The expression of ZO-1 and ER-β but not ER-α was present in both male and female gut tissues. There was no sex difference in ER-β expression, but ZO-1 expression was decreased in females compared to males. In vitro, estrogen treatment decreased ZO-1 mRNA and protein expression, ZO-1 promoter activity, IL-6 production, and NF-κB activation in human primary gut tissues or the Caco-2 cells, but increased the ER-β expression in Caco-2 cells. Consistently, plasma IL-6 levels in females were reduced relative to males in vivo. Our finding indicates that estrogen may play a role in gut tight junction expression and permeability.

Deoxycholic acid disrupts the intestinal mucosal barrier and promotes intestinal tumorigenesis

“…The statistical analysis for the immunofluorescence of ZO-1 was performed by ImageJ (Bethesda, USA). 28,29 Briefly, the image was opened with the ImageJ software. It was reversed to gray scale and the optical density was calibrated.…”

Increased systemic microbial translocation is associated with depression during early pregnancy

“…For example, during pregnancy, certain plasma estrogens increase up to 1000-fold, with a return to near prepregnancy levels generally within the first few hours postpartum (Russell et al, 2001). Importantly, studies from others and ours have also suggested that estradiol and human choionic gonadotophin (hCG) may have the ability to increase the mucosal permeability (Herr et al, 2013; Kuruca et al, 2017; Zhou et al, 2017). Consequently, the alteration of sex hormones in pregnant women with depression may result in a disruption of mucosal barriers, and subsequently ignite an elevated microbial translocation and systemic Inflammation.…”

Sexual dimorphism of cardiometabolic dysfunction: Gut microbiome in the play?

“…Similar protective effects of estrogen have been observed in the vaginal epithelium [100] . In contrast, a recent study showed that estrogen decreases tight junction protein zonula occludens 1 (ZO-1) expression in primary colonic tissues isolated from post-menopausal women and men [101] . Consistent with this finding, the effect of hormone supplementation in metabolic health of post-menopausal women contrasts to those observed in pre-menopausal women, suggesting that the loss of ovarian function due to menopause may have profound and differential impact on estrogen signaling compared to pre-menopausal women [102] , [103] , [104] .…”