Estrogen receptor β regulates endometriotic cell survival through serum and glucocorticoid regulated kinase activation

Estrogen receptor (ER) b is aberrantly overexpressed in ectopic endometriotic tissues. This study demonstrates that ERb regulates the transcription of SGK1, a kinase that promotes apoptotic resistance in endometriosis via FOXO3 inactivation.

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Authors

Diana Monsivais, Ph.D., Matthew T. Dyson, Ph.D., Ping Yin, Ph.D., Antonia Navarro, Ph.D., John S. Coon 5th, M.S., Mary Ellen Pavone, M.D., Serdar E. Bulun, M.D.

Volume 105, Issue 5, Pages 1266-1273

Abstract

Objective:

To determine the expression and biologic roles of serum and glucocorticoid–regulated kinase (SGK1) in tissues and cells from patients with endometriosis and from healthy control subjects.

Design:

Case-control.

Setting:

University research setting.

Patient(s):

Premenopausal women.

Intervention(s):

Endometriotic tissues were obtained from women with ovarian endometriosis, and normal endometrial tissues were obtained from women undergoing hysterectomy for benign conditions.

Main Outcome Measure(s):

Expression levels of SGK1, the role of SGK1 in endometriosis pathology, and regulation of SGK1 by estrogen receptor (ER) β.

Result(s):

Transcript and protein levels of SGK1 were significantly higher in endometriotic tissues and cells compared with normal endometrium. SGK1 mRNA and protein levels were stimulated by E2, by the ERβ-selective agonist diarylpropionitrile, and by prostaglandin E2. SGK1 was transcriptionally regulated by ERβ based on small interfering RNA knockdown and chromatin immunoprecipitation of ERβ followed by quantitative polymerase chain reaction. SGK1 knockdown led to increased cleavage of poly(ADP-ribose) polymerase, and SGK1 activation was correlated with the phosphorylation of FOXO3a, a proapoptotic factor.

Conclusion(s):

ERβ leads to SGK1 overexpression in endometriosis, which contributes to the survival of endometriotic lesions through inhibition of apoptosis.

Read the full text at: http://www.fertstert.org/article/S0015-0282(16)00047-9/fulltext


Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

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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