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A Tissue Culture Model of Estrogen-producing Primary Bovine Granulosa Cells
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Progesterone receptor membrane component 1 and 2 regulate granulosa cell mitosis and survival through a

John J Peluso1,2, Cindy A Pru3, Xiufang Liu1

  • 1Department of Cell Biology, University of Connecticut Health Center, Farmington, Connecticut, USA.

Biology of Reproduction
|March 17, 2019
PubMed

Insights

Progesterone receptor membrane component 1 (PGRMC1) and PGRMC2 regulate granulosa cell cycle entry. Disrupting their interaction with G3BP2 leads to nuclear factor-kappa-B (NFκB) activation and increased cell cycle progression, impacting follicular atresia.

Area of Science:

  • Reproductive Biology
  • Cell Biology
  • Molecular Endocrinology

Background:

  • Progesterone receptor membrane component 1 (PGRMC1) and PGRMC2 are key proteins in granulosa cells.
  • Disruption of PGRMC1-PGRMC2 interaction in granulosa cells can lead to cell cycle dysregulation.
  • Nuclear factor-kappa-B (NFκB) signaling plays a role in cellular processes, including cell cycle control.

Purpose of the Study:

  • To investigate the role of PGRMC1 and PGRMC2 in regulating granulosa cell cycle entry.
  • To elucidate the functional relationship between PGRMC1, PGRMC2, and NFκB/p65 signaling.
  • To determine how PGRMC1 and PGRMC2 control NFκB/p65 localization and transcriptional activity.

Main Methods:

  • Conditional deletion of Pgrmc1 in murine granulosa cells.
  • Analysis of cell cycle entry, follicular atresia, and NFκB/p65 localization.
  • Studies involving disruption of PGRMC1-PGRMC2 interactions and depletion of PGRMC1, PGRMC2, or G3BP2 in cell culture.

Main Results:

  • Conditional deletion of PGRMC1 increased granulosa cell cycle entry and follicular atresia.
  • Increased nuclear localization of NFκB/p65 was observed upon disruption of PGRMC1-PGRMC2 interaction.
  • Depletion of PGRMC1, PGRMC2, or G3BP2 enhanced NFκB transcriptional activity and cell cycle progression.

Conclusions:

  • PGRMC1 and PGRMC2 precisely control granulosa cell cycle entry.
  • These proteins regulate NFκB/p65 localization, thereby modulating its transcriptional activity.
  • The PGRMC1/PGRMC2-G3BP2 complex is crucial for maintaining granulosa cell homeostasis and preventing aberrant cell cycle progression.
Keywords:
apoptosisfollicular developmentgranulosa cellmitosisovary

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