Estrogen Receptors and Signaling in Fibroids

Role in Pathobiology and Therapeutic Implications

Mostafa A. Borahay, Mehmet R. Asoglu, Aymara Mas, Sarah Adam, Gokhan Kilic, Ayman Al-Hendy

Research output: Contribution to journalReview article

17 Citations (Scopus)

Abstract

Uterine fibroids are the most common gynecologic tumors with a significant medical and financial burden. Several genetic, hormonal, and biological factors have been shown to contribute to the development and growth of fibroid tumors. Of these factors, estrogen is particularly critical since fibroids are considered estrogen dependent because no prepubertal cases have been described in the literature and tumors tend to regress after menopause. Understanding the role of estrogen in fibroids is not only important for understanding the pathobiology of fibroids but also for the development of successful therapeutics. In this review, we discuss the types and structure of estrogen receptors (nuclear and membrane bound, including α and β receptors and G protein-coupled estrogen receptor 1 GPER1). Estrogen-signaling pathways in fibroids include genomic (direct and indirect) and nongenomic including Ras-Raf-MEK (MAPK/Erk Kinase)-mitogen-activated protein kinase (MAPK) and phosphatidylinositide 3-kinase (PI3K)-phosphatidylinositol-3,4,5-trisphosphate (PIP3)-Akt (Protein kinase B)-mammalian target of rapamycin (mTOR) pathways; shortly Ras-Raf-MEK-MAPK and PI3K-PIP3-Akt-mTOR pathways. Several aberrations in estrogen receptors and signaling pathways are implicated in fibroid pathobiology. Current therapeutic and research agents targeting ERs/signaling include gonadotropin-releasing hormone (GnRH) agonists, GnRH antagonists, aromatase inhibitors, selective ER modulators, gene therapy, and others. Future research can identify potential targets for the development of novel treatments. In particular, epigenomics of estrogen activity and individualized (precision) medicine appear to be attractive areas for future research.

Original languageEnglish (US)
Pages (from-to)1235-1244
Number of pages10
JournalReproductive Sciences
Volume24
Issue number9
DOIs
StatePublished - Sep 1 2017

Fingerprint

Leiomyoma
Estrogen Receptors
Estrogens
Mitogen-Activated Protein Kinase Kinases
Precision Medicine
Sirolimus
Gonadotropin-Releasing Hormone
Therapeutics
MAP Kinase Kinase Kinase 3
MAP Kinase Kinase 3
Therapeutic Human Experimentation
MAP Kinase Kinase Kinases
Hormone Antagonists
Proto-Oncogene Proteins c-akt
Aromatase Inhibitors
Estrogen Receptor alpha
Nuclear Envelope
Biological Factors
Cytoplasmic and Nuclear Receptors
Menopause

Keywords

  • estrogen
  • estrogen receptor
  • fibroid
  • signaling
  • treatment
  • uterine leiomyoma

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

Estrogen Receptors and Signaling in Fibroids : Role in Pathobiology and Therapeutic Implications. / Borahay, Mostafa A.; Asoglu, Mehmet R.; Mas, Aymara; Adam, Sarah; Kilic, Gokhan; Al-Hendy, Ayman.

In: Reproductive Sciences, Vol. 24, No. 9, 01.09.2017, p. 1235-1244.

Research output: Contribution to journalReview article

Borahay, Mostafa A. ; Asoglu, Mehmet R. ; Mas, Aymara ; Adam, Sarah ; Kilic, Gokhan ; Al-Hendy, Ayman. / Estrogen Receptors and Signaling in Fibroids : Role in Pathobiology and Therapeutic Implications. In: Reproductive Sciences. 2017 ; Vol. 24, No. 9. pp. 1235-1244.
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