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Updated: Feb 10, 2026

A Tissue Culture Model of Estrogen-producing Primary Bovine Granulosa Cells
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Estrogen receptor β: Potential target for therapy in adult granulosa cell tumors?

Alessandra Ciucci1, Gabriella Ferrandina1, Floriana Mascilini1

  • 1Department of Woman and Child Health, Fondazione Policlinico Universitario A. Gemelli IRCCS -Università Cattolica del Sacro Cuore, Rome, Italy.

Gynecologic Oncology
|May 23, 2018
PubMed
Abstract

Insights

Estrogen receptor beta (ERβ) plays a key role in adult granulosa cell tumors (AGCTs), potentially inhibiting apoptosis. Understanding ERβ activity is crucial for developing targeted hormonal therapies for this rare ovarian cancer.

Area of Science:

  • Gynecologic Oncology
  • Endocrinology
  • Molecular Biology

Background:

  • Adult granulosa cell tumors (AGCTs) are rare ovarian cancers originating from sex-cord stromal cells.
  • AGCTs secrete estrogens, making estrogen receptor (ER)-mediated signaling a potential therapeutic target.
  • Understanding ER status in AGCTs is vital for developing personalized hormonal treatments.

Purpose of the Study:

  • To investigate the expression and activity of estrogen receptor (ER) isoforms in adult granulosa cell tumors (AGCTs).
  • To provide molecular insights supporting personalized hormonal therapy strategies for AGCT patients.

Main Methods:

  • Immunohistochemistry was used to assess ERα, ERβ isoforms (ERβ1, ERβ2, ERβ5), progesterone receptor (PR), and androgen receptor (AR) in 20 primary and 12 recurrent AGCTs.
  • Immunofluorescence visualized the subcellular distribution of cytoplasmic receptors.
  • Proximity ligation assays (PLA) characterized in situ protein interactions involved in apoptosis.

Main Results:

  • Primary AGCTs predominantly expressed ERβ isoforms, PR, and AR, with ERα detected in only 30% of cases.
  • Recurrent tumors showed decreased AR levels.
  • Mechanistic studies revealed ERβ2, ERβ1, and AR as mitochondrial components, with ERβ2 potentially inhibiting apoptosis by interacting with apoptotic cascade proteins.

Conclusions:

  • ERβ likely contributes to AGCT pathogenesis.
  • Further research into ER-mediated pathways is essential before initiating hormonal treatments for AGCT.
  • Targeting ER pathways may offer novel therapeutic avenues for adult granulosa cell tumors.
Keywords:
ERβEstradiolHormonal therapyMitochondriaOvaryPersonalized medicine

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