Progesterone receptors: form and function in brain.
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.
Brinton
Roberta Diaz
RD
Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, School of Pharmacy, 1985 Zonal Avenue, Los Angeles, CA 90089, USA. rbrinton@usc.edu
Thompson
Richard F
RF
Foy
Michael R
MR
Baudry
Michel
M
Wang
Junming
J
Finch
Caleb E
CE
Morgan
Todd E
TE
Pike
Christian J
CJ
Mack
Wendy J
WJ
Stanczyk
Frank Z
FZ
Nilsen
Jon
J
D000544:Alzheimer Disease / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D001923:Brain Chemistry; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008540:Meiosis / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D008938:Mitosis / Q000187:drug effects; D009457:Neuroglia / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology; D020033:Protein Isoforms / Q000032:analysis; D011980:Receptors, Progesterone / Q000502:physiology*
D018696:Neuroprotective Agents; D020033:Protein Isoforms; D011980:Receptors, Progesterone; C101118:progesterone receptor A; C097314:progesterone receptor B