A truncated progesterone receptor (PR-M) localizes to the mitochondrion and controls cellular respiration.

Journal Article (Journal Article)

The cDNA for a novel truncated progesterone receptor (PR-M) was previously cloned from human adipose and aortic cDNA libraries. The predicted protein sequence contains 16 unique N-terminal amino acids, encoded by a sequence in the distal third intron of the progesterone receptor PR gene, followed by the same amino acid sequence encoded by exons 4 through 8 of the nuclear PR. Thus, PR-M lacks the N terminus A/B domains and the C domain for DNA binding, whereas containing the hinge and hormone-binding domains. In this report, we have localized PR-M to mitochondria using immunofluorescent localization of a PR-M-green fluorescent protein (GFP) fusion protein and in Western blot analyses of purified human heart mitochondrial protein. Removal of the putative N-terminal mitochondrial localization signal obviated association of PR-M with mitochondria, whereas addition of the mitochondrial localization signal to green fluorescent protein resulted in mitochondrial localization. Immunoelectron microscopy and Western blot analysis after mitochondrial fractionation identified PR-M in the outer mitochondrial membrane. Antibody specificity was shown by mass spectrometry identification of a PR peptide in a mitochondrial membrane protein isolation. Cell models of overexpression and gene silencing of PR-M demonstrated a progestin-induced increase in mitochondrial membrane potential and an increase in oxygen consumption consistent with an increase in cellular respiration. This is the first example of a truncated steroid receptor, lacking a DNA-binding domain that localizes to the mitochondrion and initiates direct non-nuclear progesterone action. We hypothesize that progesterone may directly affect cellular energy production to meet the increased metabolic demands of pregnancy.

Full Text

Duke Authors

Cited Authors

  • Dai, Q; Shah, AA; Garde, RV; Yonish, BA; Zhang, L; Medvitz, NA; Miller, SE; Hansen, EL; Dunn, CN; Price, TM

Published Date

  • May 2013

Published In

Volume / Issue

  • 27 / 5

Start / End Page

  • 741 - 753

PubMed ID

  • 23518922

Pubmed Central ID

  • PMC3634113

Electronic International Standard Serial Number (EISSN)

  • 1944-9917

Digital Object Identifier (DOI)

  • 10.1210/me.2012-1292


  • eng

Conference Location

  • United States