Membrane-initiated signaling of estrogen in the brain.
It is well known that many of the actions of estrogen in the central nervous system are mediated via intracellular receptor/transcription factors that interact with steroid response elements on target genes. However, there now exists compelling evidence for membrane steroid receptors for estrogen in hypothalamic and other brain neurons. It is not well understood how estrogen signals via membrane receptors, and how these signals influence not only membrane excitability but also gene transcription in neurons. Indeed, it has been known for some time that estrogen can rapidly alter neuronal activity within seconds, indicating that some cellular effects can occur via membrane-delimited events. In addition, estrogen can affect second messenger systems including calcium mobilization and a plethora of kinases to alter cell signaling. Therefore, this review considers our current knowledge of rapid membrane-initiated and intracellular signaling by estrogen in the brain, and the nature of receptors involved and how they contribute to homeostatic functions.
Rønnekleiv
Oline K
OK
Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, Oregon 97239-3098, USA. ronnekle@ohsu.edu
Malyala
Anna
A
Kelly
Martin J
MJ
D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism* / Q000494:pharmacology; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009490:Neurosecretory Systems / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D020239:Receptor Cross-Talk; D011956:Receptors, Cell Surface / Q000819:agonists / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000819:agonists / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000378:metabolism; D012098:Reproduction / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic
D017362:Cyclic AMP Response Element-Binding Protein; D004967:Estrogens; D036341:Intercellular Signaling Peptides and Proteins; D015221:Potassium Channels; D011956:Receptors, Cell Surface; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D017978:Receptors, Growth Factor; D007987:Gonadotropin-Releasing Hormone; D011333:Pro-Opiomelanocortin; D043802:GTP-Binding Protein alpha Subunits, Gq-G11