Extra-nuclear estrogen receptor GPR30 regulates serotonin function in rat hypothalamus.
Extra-nuclear estrogen receptor GPR30 regulates serotonin function in rat hypothalamus.
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DOI：
10.1016/j.neuroscience.2008.11.028
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发表时间：
2009-02-18
期刊：
影响因子：
3.3
通讯作者：
Muma NA
中科院分区：
文献类型：
--
作者：
Xu H;Qin S;Carrasco GA;Dai Y;Filardo EJ;Prossnitz ER;Battaglia G;Doncarlos LL;Muma NA
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 one to two 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.
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DOI：
10.1073/pnas.95.6.3281
发表时间：
1998-03-17
影响因子：
11.1
作者：
Alves, SE;Lopez, V;Weiland, NG
通讯作者：
Weiland, NG
影响因子：
--
作者：
Filardo, EJ;Quinn, JA;Bland, KI
通讯作者：
Bland, KI
影响因子：
4.7
作者：
Raap, DK;DonCarlos, L;Van de Kar, LD
通讯作者：
Van de Kar, LD
影响因子：
3.3
作者：
Carrasco, GA;Barker, SA;Van De Kar, LD
通讯作者：
Van De Kar, LD
影响因子：
7.6
作者：
Lerer, B;Gelfin, Y;Newman, ME
通讯作者：
Newman, ME