Metabolic Events Controlling Ovarian Steroidogenesis
控制卵巢类固醇生成的代谢事件
基本信息
- 批准号:9240226
- 负责人:
- 金额:$ 14.99万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-08-11 至 2020-04-30
- 项目状态:已结题
- 来源:
- 关键词:AcuteAdenosine MonophosphateBiological ModelsCapsid ProteinsCattleCell Differentiation processCellsCholesterolContraceptive methodsCyclic AMP-Dependent Protein KinasesDevelopmentDiseaseEmbryoEndocrineEnergy-Generating ResourcesEventFatty AcidsFertilityGenerationsGoalsGonadotropinsGranulosa-Lutein CellsHormone ResponsiveHormonesHumanIn VitroKnowledgeLengthLightLipidsLongevityLuteal CellsLuteal PhaseLuteinizationLuteinizing HormoneMammalsMetabolicModelingMono-SOrganellesOvarianOvarian FollicleOvaryPituitary GonadotropinsPopulationPregnancyPregnancy MaintenancePregnancy lossProductionProgesteroneProtein KinaseProteinsProteomicsRegulationResearchRodentRoleSignal TransductionSiteSomatic CellSourceSteroid biosynthesisSteroidsTestingTheca-Lutein CellsTissuesUp-RegulationWomancell typecorpus luteumdesignexperimental studyfolliculogenesisgranulosa cellhormone sensitivityhuman tissuein vitro Modelin vivoinnovationinsightmetabolomicsnovelnovel strategiesnovel therapeutic interventiontheca cell
项目摘要
The secretion of progesterone is a primary function of the corpus luteum (CL) and a prerequisite for normal
maintenance of pregnancy in all mammals. The coordinated differentiation of granulosa cells (GC) and theca
cells (TC) into a functional CL is required for fertility. The single most important factor involved in regulating
the secretion of progesterone in the CL, irrespective of species, is luteinizing hormone (LH). This pituitary
gonadotropin induces luteinization of GC and TC, formation of the CL, and is capable of extending the
functional life span of the CL. Secretion of progesterone is absolutely required for establishment and
maintenance of pregnancy and inadequate progesterone secretion contributes to early pregnancy loss in
women and cattle, the two model systems employed in this project. Despite substantial scientific progress
achieved in understanding the initial events leading to the differentiation of granulosa cells, little is known
about the differentiation of theca cells into functional luteal cells. This incomplete knowledge interferes with
the development of novel therapeutic interventions to enhance CL function (steroidogenesis), provide
contraception, and ultimately to control fertility. Recent developments in other fields of research have shed
light on the composition and role of intracellular lipid droplets as dynamic contributors to metabolic events
and disease states. These understudied organelles are prominent components of steroidogenic cells but
almost nothing is known about their role in the ovary. Despite their differences, both GC and TC accumulate
lipid droplets (LD) during CL formation, presumptively for storage of the steroid precursor, cholesterol, and
cellular energy in the form of fatty acids. The composition and precise function of LDs likely differs between
these two cells because of their unique origins and functions. There is a gap in our knowledge of the formation,
composition, and function of LDs in ovarian steroidogenic cells. This proposal will test the hypothesis that LDs
provide a metabolic or hormone-sensitive organelle which can provide cellular energy and/or store and
mobilize substrate for progesterone synthesis. We will employ state-of-the-art lipidomic, metabolomics and
proteomic analysis to examine LDs and metabolic events driven by LH in differentiating bovine granulosa
cells and theca cells and human granulosa-luteal cells. Experiments will determine the role of protein kinase
A (PKA) and adenosine monophosphate activated protein kinase (AMPK) in controlling cellular metabolic
activities that either enhance or inhibit progesterone synthesis. Our long-term objectives are to fully
understand the cellular mechanisms of action of gonadotropins and the regulation of steroidogenesis. The
short-term goals of this research are to discover new signaling events initiated by LH and to determine how
these novel mechanisms contribute to innovative strategies for enhancing progesterone synthesis, fertility,
and contraception.
黄体酮的分泌是黄体(CL)的主要功能和正常的先决条件
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)
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JOHN S DAVIS其他文献
JOHN S DAVIS的其他文献
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{{ truncateString('JOHN S DAVIS', 18)}}的其他基金
Elucidating the Role of YAP and TAZ in the Aging Human Ovary
阐明 YAP 和 TAZ 在人类卵巢衰老中的作用
- 批准号:
10722368 - 财政年份:2023
- 资助金额:
$ 14.99万 - 项目类别:
BLRD Research Career Scientist Award Application
BLRD 研究职业科学家奖申请
- 批准号:
10360744 - 财政年份:2021
- 资助金额:
$ 14.99万 - 项目类别:
BLRD Research Career Scientist Award Application
BLRD 研究职业科学家奖申请
- 批准号:
10512068 - 财政年份:2021
- 资助金额:
$ 14.99万 - 项目类别:
Signals controlling tissues homeostasis in the ovary
控制卵巢组织稳态的信号
- 批准号:
10509395 - 财政年份:2019
- 资助金额:
$ 14.99万 - 项目类别:
Signals controlling tissues homeostasis in the ovary
控制卵巢组织稳态的信号
- 批准号:
9780784 - 财政年份:2019
- 资助金额:
$ 14.99万 - 项目类别:
Signals controlling tissues homeostasis in the ovary
控制卵巢组织稳态的信号
- 批准号:
10421249 - 财政年份:2019
- 资助金额:
$ 14.99万 - 项目类别:
Signals controlling tissues homeostasis in the ovary
控制卵巢组织稳态的信号
- 批准号:
10044408 - 财政年份:2019
- 资助金额:
$ 14.99万 - 项目类别:
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