The Role of a Mitochondrial Progesterone Receptor (PR-M) in Progesterone Action

Historically, progesterone functions to regulate gene expression via two nuclear progesterone receptors (PR-B and PR-A). Yet, actions of progesterone independent of gene regulation have been observed for decades. These are based on progesterone induced cellular events that occur too rapidly to involve gene transcription or in cells lacking active gene transcription such as mature spermatozoa. Understanding of these "nongenomic" effects has been slowed by the lack of identification of specific receptors. Previous discovery of a mitochondrial progesterone receptor, PR-M, has opened up the possibility of direct, ligand-dependent modulation of mitochondrial activity. In this article, we review the current knowledge of PR-M and speculate on possible physiologic and pathophysiologic actions.