ROLE OF HORMONES IN THE PROCESSING OF NEURONAL PEPTIDES

激素在神经元肽加工中的作用

• 批准号: 3151536
• 负责人: AYALLA BARNEA
• 金额: $ 14.68万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-06-01 至 1988-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3151536
• 关键词: atomic absorption spectrometry; bioenergetics; brain mapping; chemical reaction; copper; homeostasis; hormone regulation /control mechanism; median eminence; metal metabolism; metallothionein; neural information processing; neuroendocrine system; neurons; peptide hormone; peptide hormone biosynthesis; potassium; radioimmunoassay; radiotracer; secretion; sodium; steroid hormone

The goal of this research proposal is to elucidate the mechanisms underlying LHRH release from hypothalamic neurons and its regulation by steroid hormones. Our working hypothesis (conceived as a result of our studies conducted during the period of previous grant support) is that copper, released from neurons impinging on LHRH neurons, is taken up by the LHRH neuron, interacts with the secretory granules and this interaction leads to release of the peptide. Steroids regulate LHRH release by modifying copper action on LHRH neuron and/or copper release from other neurons. Our first objective is to elucidate the biochemical mechanism of the process of copper-stimulated release of LHRH, using explants of the median eminence as a model system. To achieve this goal, we will characterize the time course, dose response and the requirements for energy, Na+, and granule -SH. The second objective is to elucidate the mechanisms by which steroids regulate LHRH release from LHRH neurons of female and male rats. To achieve this goal, we will study the effects of steroids on the process of copper-stimulated release of LHRH. To examine the specificity of this effect of steroids, we will examine in parallel, the effects of steroids on K+-stimulated release of LHRH; a process distinct from that stimulated by copper. The third objective is to define the biochemical mechanisms underlying copper homeostasis in the brain. To achieve this goal, using K+-stimulated release from brain slices as a model, we will characterize the process of copper release and its regional distribution in the brain. In addition, we will investigate the uptake, subcellular distribution and release of newly taken up [Cu64]. Once these biochemical parameters are defined, we will utilize them to achieve the goals of our fourth objective - to elucidate the mechanism by which steroids (gonadal and adrenal) regulate copper homeostasis in the brain. An understanding of the mechanisms by which steroids regulate LHRH release, through regulation of the process of copper-stimulated release of LHRH and of copper release per se, will provide insight into integrative regulatory processes in the brain and hence, into developmental and hormonally regulated brain functions.

本研究计划的目的是阐明其机制

项目成果

The isolation and measurement of luteinizing hormone-releasing hormone (LHRH) from the rat testis.

大鼠睾丸中黄体生成素释放激素（LHRH）的分离和测定。

• DOI: 10.1016/0303-7207(85)90104-2
• 发表时间: 1985
• 期刊: Molecular and cellular endocrinology
• 影响因子: 4.1
• 作者: Hedger,MP;Robertson,DM;Browne,CA;deKretser,DM
• 通讯作者: deKretser,DM

Effects of castration and maturational age of male rats on the process of copper-stimulated release of luteinizing hormone releasing hormone from median eminence explants: evidence that androgens increase the affinity of the copper-interactive sites for c

雄性大鼠去势和成熟年龄对铜刺激的中隆外植体释放黄体生成素释放激素过程的影响：雄激素增加铜相互作用位点对 c 的亲和力的证据

• DOI: 10.1159/000124219
• 发表时间: 1985
• 期刊: Neuroendocrinology
• 影响因子: 4.1
• 作者: Colombani-Vidal,M;Barnea,A
• 通讯作者: Barnea,A

Comparison of the effects of ATP, Mg2+, and MgATP on the release of luteinizing hormone-releasing hormone from isolated hypothalamic granules.

比较 ATP、Mg2 和 MgATP 对分离的下丘脑颗粒释放黄体生成素释放激素的影响。

• DOI: 10.1111/j.1471-4159.1982.tb08664.x
• 发表时间: 1982
• 期刊: Journal of neurochemistry
• 影响因子: 4.7
• 作者: Burrows,GH;Barnea,A
• 通讯作者: Barnea,A

Copper stimulation of LHRH release from median eminence explants. I. A divalent metal specific process that does not require extracellular calcium.

铜刺激正中隆起外植体释放 LHRH。

• DOI: 10.1159/000124601
• 发表时间: 1986
• 期刊: Neuroendocrinology
• 影响因子: 4.1
• 作者: Colombani-Vidal,M;Barnea,A
• 通讯作者: Barnea,A

Apparent co-sequestration of immunoreactive corticotropin, alpha-melanotropin, and gamma-lipotropin in hypothalamic granules.

下丘脑颗粒中免疫反应性促肾上腺皮质激素、α-促黑素和γ-促脂激素的明显共螯合。

• DOI: 10.1111/j.1471-4159.1981.tb01703.x
• 发表时间: 1981
• 期刊: Journal of neurochemistry
• 影响因子: 4.7
• 作者: Barnea,A;Cho,G;Porter,JC
• 通讯作者: Porter,JC