Progesterone receptors: form and function in brain.

TitleProgesterone receptors: form and function in brain.
Publication TypeJournal Article
Year of Publication2008
AuthorsBrinton RDiaz, Thompson RF, Foy MR, Baudry M, Wang J, Finch CE, Morgan TE, Pike CJ, Mack WJ, Stanczyk FZ, Nilsen J
JournalFront Neuroendocrinol
Date Published2008 May
KeywordsAlzheimer Disease, Animals, Brain, Brain Chemistry, Cell Proliferation, Female, Humans, Male, Meiosis, Memory, Mitosis, Neuroglia, Neuronal Plasticity, Neuroprotective Agents, Protein Isoforms, Receptors, Progesterone

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 7TMPRbeta 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.

Alternate JournalFront Neuroendocrinol
PubMed ID18374402
PubMed Central IDPMC2398769
Grant ListP01 AG026572 / AG / NIA NIH HHS / United States
P01 AG026572-02 / AG / NIA NIH HHS / United States
P01AG026572 / AG / NIA NIH HHS / United States
Faculty Member Reference: 
Roberta Diaz Brinton, Ph.D