Journal article
Extra-nuclear estrogen receptor GPR30 regulates serotonin function in rat hypothalamus
Neuroscience, Vol.158(4), pp.1599-1607
02/18/2009
DOI: 10.1016/j.neuroscience.2008.11.028
PMCID: PMC2747636
PMID: 19095043
Abstract
Selective serotonin reuptake inhibitors (SSRIs), such as Prozac®, are used to treat mood disorders. SSRIs attenuate (i.e. desensitize) serotonin 1A (5-HT1A) receptor signaling, as demonstrated in rats through decreased release of oxytocin and adrenocorticotropin hormone (ACTH) following 5-HT1A receptor stimulation. Maximal therapeutic effects of SSRIs for treatment of mood disorders, as well as effects on hypothalamic 5-HT1A receptor signaling in animals, take 1 to 2 weeks to develop. Estradiol also attenuates 5-HT1A receptor signaling, but, in rats, these effects occur within 2 days; thus, estrogens or selective estrogen receptor modulators may serve as useful short-term tools to accelerate desensitization of 5-HT1A receptors in response to SSRIs if candidate estrogen receptor targets in the hypothalamus are identified. We found high levels of GPR30, which has been identified recently as a pertussis-toxin (PTX) sensitive G-protein-coupled estrogen receptor, in the hypothalamic paraventricular nucleus (PVN) of rats. Double-label immunohistochemistry revealed that GPR30 co-localizes with 5-HT1A receptors, corticotrophin releasing factor (CRF) and oxytocin in neurons in the PVN. Pretreatment with PTX to the PVN before peripheral injections of 17-β-estradiol 3-benzoate completely prevented the reduction of the oxytocin response to the 5-HT1A receptor agonist, (+)-8-hydroxy-2-dipropylaminotetralin (DPAT). Treatment with the selective GRP30 agonist, G-1, attenuated 5-HT1A receptor signaling in the PVN as measured by an attenuated oxytocin (by 29%) and ACTH (by 31%) response to DPAT. This study indicates that a putative extra-nuclear estrogen receptor, GPR30, may play a role in estradiol-mediated attenuation of 5-HT1A receptor signaling, and potentially in accelerating the effects of SSRIs in treatment of mood disorders.
Details
- Title: Subtitle
- Extra-nuclear estrogen receptor GPR30 regulates serotonin function in rat hypothalamus
- Creators
- H Xu - Department of Pharmacology and Experimental Therapeutics, Loyola University Chicago School of Medicine, Maywood, IL 60153, USAS Qin - Department of Pharmacology and Toxicology, School of Pharmacy, 5064 Malott Hall, University of Kansas, Lawrence, KS 66045, USAG.A Carrasco - Department of Pharmacology and Toxicology, School of Pharmacy, 5064 Malott Hall, University of Kansas, Lawrence, KS 66045, USAY Dai - Department of Pharmacology and Experimental Therapeutics, Loyola University Chicago School of Medicine, Maywood, IL 60153, USAE.J Filardo - Department of Medicine, Rhode Island Hospital and Brown University School of Medicine, Providence, RI 02903, USAE.R Prossnitz - Department of Cell Biology and Physiology and the Cancer Research and Treatment Center, University of New Mexico Health Science Center, Albuquerque, NM 87131, USAG Battaglia - Department of Pharmacology and Experimental Therapeutics, Loyola University Chicago School of Medicine, Maywood, IL 60153, USAL.L DonCarlos - Department of Cell Biology, Neurobiology and Anatomy, Loyola University Chicago School of Medicine, Maywood, IL 60153, USAN.A Muma - Department of Pharmacology and Toxicology, School of Pharmacy, 5064 Malott Hall, University of Kansas, Lawrence, KS 66045, USA
- Resource Type
- Journal article
- Publication Details
- Neuroscience, Vol.158(4), pp.1599-1607
- DOI
- 10.1016/j.neuroscience.2008.11.028
- PMID
- 19095043
- PMCID
- PMC2747636
- NLM abbreviation
- Neuroscience
- ISSN
- 0306-4522
- eISSN
- 1873-7544
- Publisher
- Elsevier BV
- Language
- English
- Date published
- 02/18/2009
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics; Surgery; Internal Medicine
- Record Identifier
- 9984051778102771
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