Progesterone receptors: Form and function in brain

Roberta Diaz Brinton, Richard F. Thompson, Michael R. Foy, Michel Baudry, Jun Ming Wang, Caleb E. Finch, Todd E. Morgan, Christian J. Pike, Wendy J. Mack, Frank Z. Stanczyk, Jon Nilsen

Research output: Contribution to journalReview articlepeer-review

531 Scopus citations


Emerging data indicate that progesterone has multiple non-reproductive functions in the central nervous system to regulate cognition, mood, inflammation, mitochondrial function, neurogenesis and regeneration, myelination and recovery from traumatic brain injury. Progesterone-regulated neural responses are mediated by an array of progesterone receptors (PR) that include the classic nuclear PRA and PRB receptors and splice variants of each, the seven transmembrane domain 7TMPRβ and the membrane-associated 25-Dx PR (PGRMC1). These PRs induce classic regulation of gene expression while also transducing signaling cascades that originate at the cell membrane and ultimately activate transcription factors. Remarkably, PRs are broadly expressed throughout the brain and can be detected in every neural cell type. The distribution of PRs beyond hypothalamic borders, suggests a much broader role of progesterone in regulating neural function. Despite the large body of evidence regarding progesterone regulation of reproductive behaviors and estrogen-inducible responses as well as effects of progesterone metabolite neurosteroids, much remains to be discovered regarding the functional outcomes resulting from activation of the complex array of PRs in brain by gonadally and/or glial derived progesterone. Moreover, the impact of clinically used progestogens and developing selective PR modulators for targeted outcomes in brain is a critical avenue of investigation as the non-reproductive functions of PRs have far-reaching implications for hormone therapy to maintain neurological health and function throughout menopausal aging.

Original languageEnglish (US)
Pages (from-to)313-339
Number of pages27
JournalFrontiers in Neuroendocrinology
Issue number2
StatePublished - May 2008
Externally publishedYes


  • 25-Dx PR
  • 7TMPR
  • Alzheimer's disease
  • Hormone therapy
  • Inflammation
  • Neurogenesis
  • PGRMC1
  • PRA
  • PRB
  • Progesterone

ASJC Scopus subject areas

  • Endocrine and Autonomic Systems


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