Estrogen Supports Urothelial Defense Mechanisms

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Science Translational Medicine  19 Jun 2013:
Vol. 5, Issue 190, pp. 190ra80
DOI: 10.1126/scitranslmed.3005574

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Urothelial Defense Tug-of-War

It is well known that urinary tract infections (UTIs) are common in women, but which women are at more risk of UTIs is still far from certain, with some studies suggesting that it’s younger women, and others showing evidence of increased risk after menopause. Now, a study by Lüthje and coauthors suggests that both of those views may be partially correct and demonstrates the mechanisms for each.

To understand how estrogen contributes to UTI pathogenesis, the authors examined cells from the urothelium (bladder lining) of menstruating women and older, postmenopausal subjects, studying the postmenopausal women before and after a 2-week period of estrogen supplementation. Then, to determine the mechanistic basis for their observations, they studied urothelial cells in an estrogen-depleted mouse model and in vitro. Thus, they demonstrated that estrogen has a protective effect on the urothelium, stimulating production of antimicrobial peptides and strengthening the attachment between urothelial cells. At the same time, the authors found that estrogen also increases the amount of bacteria taken up inside the urothelial cells.

On the basis of the findings of Lüthje et al., one can conclude that young women may experience a greater incidence of UTIs because the high-estrogen environment increases the risk of bacterial invasion of the urothelium. Conversely, postmenopausal women may have more difficulty fighting off the infections because of their decreased production of antimicrobial peptides and diminished integrity of the urothelial lining. Additional studies of human and animal subjects will be needed to learn more about the molecular mechanism of estrogen’s effects on the urothelium and understand what determines the balance between its pro- and anti-UTI effects. However, this line of research does advance us closer to understanding and eventually helping prevent the problem of recurrent UTIs in women.

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