A reciprocal relationship between alcohol and the p450 enzyme aromatase
酒精和 p450 芳香酶之间的相互关系
基本信息
- 批准号:10386167
- 负责人:
- 金额:$ 4.6万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-30 至 2024-09-29
- 项目状态:已结题
- 来源:
- 关键词:AcuteAddressAdipose tissueAlcohol consumptionAlcoholsAnxietyAromataseAromatase InhibitionAromatase InhibitorsAttenuatedAutomobile DrivingBathingBehaviorBehavioralBrainBrain regionChronicClinicalCorticotropin-Releasing HormoneCytochrome P450DataElectrophysiology (science)EnzymesEstradiolEstrogensFemaleFeminizationFrequenciesFulvestrantGlutamatesGonadal structureHeavy DrinkingLaboratoriesLearningLetrozoleLinkLiverLoxP-flanked alleleMaintenanceMalignant NeoplasmsMeasurementMeasuresMediatingMolecular GeneticsMusNeuronsOrganOvaryPathologicPeripheralPharmacologyPhysiologyPlasmaPlayProcessPublic HealthRecording of previous eventsResearchRewardsRisk FactorsRoleSignal TransductionSiteSocietiesSourceStressStructure of terminal stria nuclei of preoptic regionSucroseSynaptic TransmissionTechniquesTestosteroneTimeTissuesUp-RegulationViralWaterWorkaddictionalcohol abuse therapyalcohol behavioralcohol exposurealcohol measurementalcohol use disorderanastrozolebinge drinkingbrain tissuechronic alcohol ingestiondrinkingdrinking behaviordrinking waterhealth economicsinhibitor/antagonistknock-downmalemenpostsynapticprotein expressionreceptorreceptor expressionrecruitrelating to nervous systemresponsesexsocialsteroid hormonetransmission process
项目摘要
Project Summary
Excessive alcohol consumption is a significant problem in our society that causes far-reaching health, economic,
and personal issues. The steroid hormone estrogen (17β-estradiol; E2) is synthesized in organs throughout the
body, including the brain, via the conversion of testosterone into E2 by the cytochrome p450 enzyme aromatase
(AROM). E2 made in the ovaries has been shown to increase reward sensitivity, learning, and alcohol
consumption. In addition, there is clinical evidence that chronic alcohol consumption may upregulate AROM
activity and E2 synthesis, suggesting that additional sources of AROM may contribute to alcohol-related
behavior. I find that acute pharmacological AROM inhibition reduces alcohol drinking in males following 3 weekly
cycles of binge drinking and in females following 10 cycles. The bed nucleus of the stria terminalis (BNST), a
brain region highly associated with reward, anxiety, and addiction, is a known source of E2 receptor expression
and E2 transmission. Our laboratory has found that E2 administration to the BNST increases binge alcohol
consumption and increases glutamate release onto BNST corticotropin releasing factor (CRF) neurons. The
overarching hypothesis of this proposal is that there is a reciprocal relationship between alcohol and AROM,
such that alcohol drinking recruits increased AROM expression, resulting in increased E2 tone in the BNST that
promotes further binge alcohol consumption. I have developed a comprehensive research plan to address the
scientific questions derived from this hypothesis. In Aim 1, I will execute electrophysiological and behavioral
techniques to examine whether alcohol-induced E2 acts in the BNST to promote drinking. In Aim 2, I will
determine sites of increased AROM in the brain and body and evaluate their roles in binge drinking behavior
using electrophysiological, molecular, genetic, and behavioral techniques. The proposed work seeks to provide
information on the mechanisms driving binge alcohol consumption and has significant implications for the
widespread public health issue of excessive alcohol drinking.
项目摘要
过度饮酒是我们社会中的一个重大问题,它对健康、经济、
和个人问题类固醇激素雌激素(17β-雌二醇; E2)是在整个器官中合成的。
身体,包括大脑,通过细胞色素p450芳香酶将睾酮转化为E2
(AROM)。卵巢中产生的E2已被证明可以增加奖励敏感性,学习和酒精
消费此外,有临床证据表明,长期饮酒可能会上调AROM
活性和E2合成,这表明AROM的额外来源可能有助于酒精相关的
行为我发现急性药理学AROM抑制可以减少男性每周3次的饮酒量
酗酒周期和女性10个周期后。终纹床核(BNST),
与奖赏、焦虑和成瘾高度相关的大脑区域是E2受体表达的已知来源
E2传输我们的实验室发现,给予BNST E2会增加酗酒
消耗和增加谷氨酸释放到BNST促肾上腺皮质激素释放因子(CRF)神经元。的
该建议的首要假设是酒精和AROM之间存在相互关系,
这样,饮酒新兵增加AROM表达,导致BNST中E2张力增加,
进一步促进酗酒。我已经制定了一个全面的研究计划,
从这个假设衍生出来的科学问题。在目标1中,我将执行电生理和行为
技术来检查酒精诱导的E2是否在BNST中起作用以促进饮酒。在目标2中,我将
确定大脑和身体中AROM增加的部位,并评估它们在酗酒行为中的作用
使用电生理学、分子、遗传和行为技术。拟议的工作旨在提供
关于驱动酗酒的机制的信息,并对
过度饮酒是一个普遍的公共卫生问题。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Lia Juliet Zallar其他文献
Lia Juliet Zallar的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Lia Juliet Zallar', 18)}}的其他基金
A reciprocal relationship between alcohol and the p450 enzyme aromatase
酒精和 p450 芳香酶之间的相互关系
- 批准号:
10681419 - 财政年份:2021
- 资助金额:
$ 4.6万 - 项目类别:
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 4.6万 - 项目类别:
Fellowship
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 4.6万 - 项目类别:
Continuing Grant
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 4.6万 - 项目类别:
Research Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 4.6万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 4.6万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 4.6万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 4.6万 - 项目类别:
EU-Funded
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 4.6万 - 项目类别:
Standard Grant
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 4.6万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 4.6万 - 项目类别:
Research Grant