NEUROENDOCRINE EFFECTS OF ALCOHOL ON PUBERTY

酒精对青春期神经内分泌的影响

• 批准号: 2682960
• 负责人: W L DEES
• 金额: $ 22.37万
• 依托单位: TEXAS A&M UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-07-01 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2682960
• 关键词: Macaca mulatta; NMDA receptors; RNase protection assay; animal puberty; drug interactions; estradiol; ethanol; hormone regulation /control mechanism; hypothalamus; insulinlike growth factor; laboratory rat; luteinizing hormone; menstrual cycle; messenger RNA; neuroendocrine system; neuropeptide Y; neurotransmitters; prolactin; radioimmunoassay; somatotropin; tissue /cell culture

The CNS plays the pivotal role in the synchronization of events leading to puberty by controlling anterior pituitary function via the secretion of hypothalamic factors, and the ovary via pituitary hormones and direct neural inputs. This being the case, a drug that is capable of affecting any one of the portions of the reproductive axis during the pubertal process could cause serious manifestations to occur, which may affect the otherwise normal series of events during pubertal development. These studies are designed to obtain information which will allow us to better understand the detrimental effects and mechanism(s) of action of ethanol (ETOH) on the pubertal process. In recent years it has been shown that the administration of either N-methyl-DL-aspartic acid (NMDA) or neuropeptide Y (NPY) will advance the pubertal process. There is also some evidence now that specific growth factors [i.e., insulin-like growth factor I (IGF-I), epidermal growth factor (BGF) and nerve growth factor (NGF)] may also be involved. In vivo and in vitro techniques will be used, following short-term and acute ETOH exposure to address the following: IN THE RAT: The overall goal is to determine what effect(s) ETOH may have on the above substances and their respective influence on puberty related events. Specifically, we will: a) assess ETOH's effects on the synthesis of their specific mRNA, and/or in some cases, receptor mRNA, via RNase protection assays. These results will be correlated with assessments of hypothalamic, pituitary and ovarian hormones, as well as with other specific indices of puberty, b) assess ETOH's effects on NMDA, NPY and growth factor-mediated secretion of specific LH and GH controlling hypothalamic peptides in vitro, c) assess ETOH's effects on their respective abilities to elicit the pulsatile secretion of LH and GH in vivo, d) assess ETOH's potential effect to alter the extrinsic ovarian innervation by altering synthesis of ovarian NGF, or the low affinity (p75) of high affinity (trkA) NGF receptors, and e) assess the in vitro effects of ETOH on IGF-I, GH and vasoactive intestinal peptide facilitory actions on ovarian steroid release. IN THE RHESUS MONKEY: The overall goal is to determine ETOH's potential effects on the pubertal process in primates. Specifically, we will: f) assess ETOH's effects on the extrinsic ovarian innervation and on the factors governing this innervation, as well as on the developmentally regulated ovarian neurons we have recently described in this species, and g) assess ETOH's effects on the timing and progression of pubertal increases in IGF-I, GH, LH and estradiol, and on the age at first menarche.

中枢神经系统在导致事件同步的过程中发挥着关键作用 通过分泌控制垂体前叶功能来控制青春期 下丘脑因素，卵巢通过垂体激素和直接 神经输入。 既然如此，一种药物就能够影响 青春期期间生殖轴的任何一部分 过程可能会导致严重的表现，这可能会影响 青春期发育期间发生的一系列正常事件。这些 研究旨在获取信息，使我们能够更好地 了解乙醇的有害影响和作用机制 （ETOH）对青春期过程的影响。 近年来的研究表明 N-甲基-DL-天冬氨酸（NMDA）或 神经肽 Y (NPY) 将促进青春期过程。还有一些 现在有证据表明特定的生长因子[即胰岛素样生长 I 因子 (IGF-I)、表皮生长因子 (BGF) 和神经生长因子 (NGF)]也可能参与其中。 体内和体外技术将 在短期和急性接触 ETOH 后使用，以解决 以下：在大鼠中：总体目标是确定什么效果 乙醇可能对上述物质及其各自的影响 青春期相关事件。 具体来说，我们将： a) 评估 ETOH 的影响 其特定 mRNA 和/或在某些情况下受体的合成 mRNA，通过 RNase 保护测定。这些结果将与 下丘脑、垂体和卵巢激素的评估，以及 与其他具体的青春期指数，b) 评估 ETOH 对 NMDA 的影响， NPY 和生长因子介导的特定 LH 和 GH 控制的分泌 体外下丘脑肽，c) 评估 ETOH 对它们的影响 分别引起 LH 和 GH 脉冲式分泌的能力 体内，d) 评估 ETOH 改变外源性卵巢的潜在作用 通过改变卵巢 NGF 的合成或低亲和力来神经支配 (p75) 高亲和力 (trkA) NGF 受体，以及 e) 评估体外 ETOH 对 IGF-I、GH 和血管活性肠肽促进剂的影响 对卵巢类固醇释放的作用。在恒河猴中：总体目标 是为了确定 ETOH 对青春期过程的潜在影响 灵长类动物。 具体来说，我们将： f) 评估 ETOH 对 卵巢外源性神经支配及其影响因素 神经支配以及发育调节的卵巢神经元 我们最近描述了这个物种，并且 g) 评估 ETOH 的影响 青春期 IGF-I、GH、LH 和 雌二醇，以及初潮年龄。