CENTRAL CONTROL OF OXYTOCIN RELEASE DURING GESTATION

妊娠期间催产素释放的集中控制

• 批准号: 6865301
• 负责人: STEVEN BEALER BEALER
• 金额: $ 29.08万
• 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 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6865301
• 关键词: antisense nucleic acid; autoradiography; clinical research; developmental nutrition; excitatory aminoacid; fos protein; gene expression; hormone inhibitor; hormone receptor; hormone regulation /control mechanism; hypothalamus; laboratory rat; lactation; neurons; neuroregulation; newborn animals; oligonucleotides; oxytocin; peptide hormone biosynthesis; pregnancy; radioimmunoassay; single cell analysis; synaptogenesis; tissue /cell culture

DESCRIPTION (provided by applicant): The overall objective of this research project is to characterize the autoregulatory functions of central oxytocin (OT) on systemic OT release during reproductive states. OT is released during parturition to aid in uterine contraction, and OT secretion during nursing is essential for milk delivery and normal growth of the offspring. Recent studies find that the central OT system is activated during gestation, and participates in behavioral, anatomical, and physiological adaptations, which contribute to successful lactation. We have found that OT receptor (OTR) binding increases during gestation, and that blockade of OTR, only during gestation, decreases milk delivery to suckling offspring, resulting in reduced weight gain. However, the mechanism(s) by which OTR blockade during gestation diminishes lactational efficiency is unknown. We will test the HYPOTHESIS that OTR stimulation during gestation is required for genetic and electrophysiological adaptations necessary for 1) increased OT synthesis and 2) OT neuron sensitivity required for adequate milk delivery in response to suckling. To test this proposal, the SPECIFIC AIMS are to determine the effects of OTR blockade DURING GESTATION on; 1) OT binding in magnocellular nuclei, 2) OT mRNA in magnocellular nuclei and OT content in the neural lobe during gestation and mid-lactation, 3) development of OT neuron membrane and synaptic adaptations characteristic of lactation, and 4) response sensitivity of OT neurons to suckling and administration of excitatory neurotransmitters. These Aims will be addressed using receptor autoradiography, biochemical measures of OT mRNA, radioimmunoassay of OT in neural lobe, dialysate, and plasma, microdialysis, electrophysiological evaluation of isolated OT cells and in hypothalamic slices, and activation of c-fos in OT neurons. These measures will be performed on virgin animals, and pregnant animals following central administration of an OT antagonist or vehicle during mid-late gestation. Increasing efficiency of lactation to ensure adequate infant growth will increase the number of breast fed infants to recommended levels, which will decrease the incidence and severity of a wide range of illnesses and pathologies.

描述（由申请人提供）：该研究项目的总体目的是表征中央催产素（OT）在生殖状态期间全身OT释放中的自动调节功能。 OT在分娩期间释放以帮助子宫收缩，而在护理过程中的OT分泌对于牛奶输送和后代正常生长至关重要。最近的研究发现，妊娠期间激活了中央OT系统，并参与行为，解剖和生理适应性，这有助于成功泌乳。我们发现，OT受体（OTR）结合在妊娠期间增加了增加，并且仅在妊娠期间，OTR的阻断会减少牛奶的递送至哺乳后代，从而减少体重增加。然而，妊娠期间OTR阻塞降低泌乳效率的机制尚不清楚。我们将测试以下假设：妊娠期间的OTR刺激是必需的遗传学和电生理适应性的1）1）增加了OT合成和2）2）对哺乳的适当牛奶递送所需的神经元敏感性。为了测试该建议，具体的目的是确定妊娠期间OTR阻断的影响； 1) OT binding in magnocellular nuclei, 2) OT mRNA in magnocellular nuclei and OT content in the neural lobe during gestation and mid-lactation, 3) development of OT neuron membrane and synaptic adaptations characteristic of lactation, and 4) response sensitivity of OT neurons to suckling and administration of excitatory neurotransmitters.这些目标将使用受体放射自显影，OT mRNA的生化测量，神经叶中OT的放射免疫分子，透析和血浆中的OT，微透析，微透析，分离的OT细胞的电生理评估，以及OT NEURONS中C-FOS的分离的OT细胞以及OT Neurors的活化。这些措施将对处女动物进行，并在中间妊娠期间进行中央拮抗剂或媒介物后进行怀孕的动物。提高泌乳效率以确保婴儿的足够生长将使婴儿的母亲数量增加到建议的水平，这将降低广泛的疾病和病理的发生率和严重程度。