Activated Glucocorticoid and Eicosanoid Pathways in Endometriosis

Gene networks that regulate prostaglandin and cortisol synthesis are altered in endometriosis, and the proinflammatory milieu of an endometriotic lesion perturbs cortisol synthesis and action.

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Authors

Diana Monsivais, M.S., Jeffrey D. Bray, Ph.D., Emily Su, M.D., Mary Ellen Pavone, M.D., Matthew T. Dyson, Ph.D., Antonia Navarro, B.S., Toshiyuki Kakinuma, M.D., Ph.D., Serdar E. Bulun, M.D.

Vol 98, Issue 1 , Pages 117-125, July 2012

Abstract

Objective:

To define altered gene expression networks in endometriosis.

Design:

Experiments using endometriotic tissues and primary cells.

Setting:

Division of Reproductive Biology Research, Northwestern University.

Patient(s):

Premenopausal women.

Intervention(s):

Matched samples of eutopic endometrium and ovarian endometriosis (n = 8 patients) were analyzed by microarray and verified in a separate set of tissues (n = 6 patients). Experiments to define signaling pathways were performed in primary endometriotic stromal cells (n = 12 patients).

Main Outcomes Measure(s):

Using a genome-wide in vivo approach, we identified 1,366 differentially expressed genes and a new gene network favoring increased glucocorticoid levels and action in endometriosis.

Result(s):

Transcript and protein levels of 11β-hydroxysteroid dehydrogenase (HSD11B1), which produces cortisol, the biologically active glucocorticoid, were strikingly higher, whereas messenger RNA (mRNA) levels of the cortisol-degrading HSD11B2 enzyme were significantly lower in endometriotic tissue. Glucocorticoid receptor mRNA and protein levels were significantly higher in endometriosis. The inflammatory cytokine tumor necrosis factor robustly induced mRNA and protein levels of HSD11B1 and glucocorticoid receptor but suppressed HSD11B2 mRNA in primary endometriotic stromal cells, suggesting that tumor necrosis factor stimulates cortisol production and action. We also uncovered a subset of genes critical for prostaglandin synthesis and degradation, which favor high eicosanoid levels and activity in endometriosis.

Conclusion(s):

The proinflammatory milieu of the endometriotic lesion stimulates cortisol synthesis and action in endometriotic lesions.

Read the full text at: http://www.fertstert.org/article/S0015-0282(12)00368-8/fulltext


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Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

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