Progesterone inhibits apoptosis in part by PGRMC1-regulated gene expression

Mol Cell Endocrinol. 2010 May 14;320(1-2):153-61. doi: 10.1016/j.mce.2010.02.005. Epub 2010 Feb 6.

Abstract

Progesterone receptor membrane component-1 (PGRMC1) is present in both the cytoplasm and nucleus of spontaneously immortalized granulosa cells (SIGCs). PGRMC1 is detected as a monomer in the cytoplasm and a DTT-resistant PGRMC1 dimer in the nucleus. Transfected PGRMC1-GFP localizes mainly to the cytoplasm and does not form a DTT-resistant dimer. Moreover, forced expression of PGRMC1-GFP increases the sensitivity of the SIGCs to progesterone (P4)'s anti-apoptotic action, indicating that the PGRMC1 monomer is functional. However, when endogenous PGRMC1 is depleted by siRNA treatment and replaced with PGRMC1-GFP, P4 responsiveness is not enhanced, although overall levels of PGRMC1 are increased. P4's anti-apoptotic action is also attenuated by actinomycin D, an inhibitor of RNA synthesis, and P4 activation of PGRMC1 suppresses Bad and increases Bcl2a1d expression. Taken together, the present studies suggest a genomic component to PGRMC1's anti-apoptotic mechanism of action, which requires the presence of the PGRMC1 dimer.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Blotting, Western
  • Cell Line, Transformed
  • Dactinomycin / pharmacology
  • Female
  • Gene Expression Regulation / drug effects*
  • Granulosa Cells / cytology
  • Granulosa Cells / drug effects
  • Granulosa Cells / metabolism
  • Green Fluorescent Proteins / metabolism
  • Heterogeneous Nuclear Ribonucleoprotein A1
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B / metabolism
  • Membrane Proteins / metabolism*
  • Progesterone / pharmacology*
  • Protein Transport / drug effects
  • RNA, Small Interfering / metabolism
  • Rats
  • Receptors, Progesterone / metabolism*
  • Recombinant Fusion Proteins / metabolism

Substances

  • Heterogeneous Nuclear Ribonucleoprotein A1
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B
  • Membrane Proteins
  • Pgrmc1 protein, rat
  • RNA, Small Interfering
  • Receptors, Progesterone
  • Recombinant Fusion Proteins
  • Green Fluorescent Proteins
  • Dactinomycin
  • Progesterone