CENTRAL CONTROL OF OXYTOCIN RELEASE DURING GESTATION

妊娠期间催产素释放的集中控制

• 批准号: 6345831
• 负责人: STEVEN BEALER BEALER
• 金额: $ 18.28万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-03-01 至 2004-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6345831
• 关键词: birth; estradiol; female; gestational age; glutamate receptor; glutamates; histamine; histamine receptor; hormone receptor; hormone regulation /control mechanism; laboratory rat; lactation; norepinephrine; ovariectomy; oxytocin; paraventricular nucleus; progesterone; supraoptic nucleus

The overall objective of this project is to identify and characterize central neurotransmitter systems that control secretion of oxytocin (OT), which is released into the systemic circulation and within the paraventricular (PVN) and supruoptic (SON) nuclei (i.e. intranuclear release) during parturition and lactation. The intranuclear release of OT is critical for normal, reflexive activation of the OT system during parturition, lactation, and late gestation. We have identified three excitatory neurotransmitter systems, norepinephrine (NE), histamine (HA), and glutamate (GLU) that interact and increase systemic and intranuclear OT release during lactation. Furthermore, changes in pregnancy-associated ovarian hormones increase OT mRNA in late pregnancy. However, the contributions of these excitatory neurotransmitter systems and ovarian hormones, as well as the importance of OT stimulation during late gestation are unknown. The experiments proposed in this application will test the overall hypothesis that activation of the OT system during late gestation results from stimulatory actions of NE, HA and GLU, as a result of the changing ovarian hormonal milieu (rise in estradiol, fall in progesterone), and that activation of the OT system at this time is necessary for the normal, reflexive release of OT subsequently during parturition and lactation. The Specific Aims are: 1) To determine the roles of excitatory transmitter systems (NE, HA, GLU) in systemic and intranuclear OT release in late gestation. 2) To test whether OT activation in late gestation occurs through actions of the ovarian hormones, and determine effects of these hormones on excitatory neurotransmitter systems. 3) To test whether prevention of OT activation in late gestation disrupts systemic and intranuclear release of OT during parturition and lactation. These studies will use in vivo microdialysis to evaluate central neurochemical release, and to administer pharmacological agents locally to magnocellular nuclei during gestation and during hormone treatment in conscious rats. These studies will contribute to the overall objectives of this program by identifying the; 1) neurotransmitters activating the OT system during pregnancy, 2) the contributions of gestation-associated ovarian hormones to OT release, and 3) importance of OT release during gestation to reflexive release which occurs during parturition and lactation.

该项目的总体目标是识别和表征控制催产素 (OT) 分泌的中枢神经递质系统，催产素在分娩过程中释放到体循环以及室旁核 (PVN) 和视上核 (SON) 内（即核内释放）和哺乳期。 OT 的核内释放对于分娩、哺乳和妊娠后期 OT 系统的正常反射激活至关重要。 我们已经确定了三种兴奋性神经递质系统：去甲肾上腺素 (NE)、组胺 (HA) 和谷氨酸 (GLU)，它们在哺乳期间相互作用并增加全身和核内 OT 的释放。此外，妊娠晚期卵巢激素的变化会增加 OT mRNA。 然而，这些兴奋性神经递质系统和卵巢激素的贡献以及妊娠晚期 OT 刺激的重要性尚不清楚。 本申请中提出的实验将检验总体假设，即妊娠晚期 OT 系统的激活是由于 NE、HA 和 GLU 的刺激作用引起的，这是卵巢激素环境变化（雌二醇上升，黄体酮下降）的结果，此时 OT 系统的激活对于随后在分娩和哺乳期间正常、反射性释放 OT 是必要的。 具体目标是： 1) 确定兴奋性递质系统（NE、HA、GLU）在妊娠晚期全身和核内 OT 释放中的作用。 2) 测试妊娠晚期OT激活是否通过卵巢激素的作用发生，并确定这些激素对兴奋性神经递质系统的影响。 3) 测试妊娠晚期预防 OT 激活是否会扰乱分娩和哺乳期间 OT 的全身和核内释放。 这些研究将使用体内微透析来评估中枢神经化学物质的释放，并在妊娠期间和清醒大鼠的激素治疗期间向大细胞核局部施用药物。 这些研究将通过确定以下内容来促进该计划的总体目标： 1) 妊娠期间神经递质激活 OT 系统，2) 妊娠相关卵巢激素对 OT 释放的贡献，3) 妊娠期间 OT 释放对分娩和哺乳期间发生的反射性释放的重要性。