IMMUNIZATION AGAINST ACTH AND PARTURITION

针对 ACTH 和分娩的免疫接种

• 批准号: 6402704
• 负责人: DEAN MYERS
• 金额: $ 7.28万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6402704
• 关键词: active immunization; adrenocorticotropic hormone; baboons; birth; hormone regulation /control mechanism

The objective of this proposal is to directly, actively immunize the baboon fetus against adrenocorticotropic hormone (ACTH) and to determine the effect of immunoneutralization of ACTH on both fetal adrenocortical function (dehydroepiandrosterone sulfate [DHEAS] and cortisol synthesis) and the length of gestation. The primate fetal adrenal cortex is the essential source of androgen for placental aromatization to estrogen. Estrogen production is integral in regulating the molecular and biophysical cascaded that leads to birth in primates. Despite the importance of the primate fetal adrenal as the source of androgen precursor for estrogen formation, the role of the primate fetus in the process of parturition remains unresolved. We propose to actively immunize fetal baboons against ACTH, the major peptide regulating cortisol and DHEA production in the primate fetus. Active immunization has been employed as a technique for examining the role of endogenous peptide and protein hormones in adults of various species. Immunization of the baboon fetus in utero provides an elegant approach to critically examine the role of the fetal hypothalamo- pituitary adrenal axis in initiating the events of normal term labor and delivery in a primate. This proposal brings together investigators with expertise in the endocrinology and biology of parturition, immunology of non human primates, and maternal fetal medicine to advance the use of active immunization of the primate fetus to directly address a critical question, namely, what is the role of fetal ACTH in regulating adrenocortical development related to parturition in a non-human primate? While advances have been made in the treatment and survival rate of preterm infants, the prevalence of preterm birth (approximately 9-10 percent) has not declined in the United States, Canada or other developed countries. Premature birth continues to be a major cause of infant mortality and is associated with increased risk o f neurological and other deficits. Identifying mechanisms that initiate the onset of normal term labor and delivery will lead to the development of better strategies for preventing premature birth.

该提案的目的是直接、积极地对狒狒胎儿进行促肾上腺皮质激素 (ACTH) 免疫，并确定 ACTH 免疫中和对胎儿肾上腺皮质功能（硫酸脱氢表雄酮 [DHEAS] 和皮质醇合成）和妊娠长度的影响。 灵长类动物胎儿肾上腺皮质是胎盘芳香化为雌激素的雄激素的重要来源。 雌激素的产生对于调节导致灵长类动物出生的分子和生物物理级联反应至关重要。 尽管灵长类动物胎儿肾上腺作为雌激素形成的雄激素前体来源很重要，但灵长类动物胎儿在分娩过程中的作用仍未解决。我们建议对狒狒胎儿进行主动免疫，以抵抗 ACTH，ACTH 是调节灵长类胎儿皮质醇和 DHEA 产生的主要肽。 主动免疫已被用作检查内源性肽和蛋白质激素在不同物种的成虫中的作用的技术。 子宫内狒狒胎儿的免疫提供了一种优雅的方法来严格检查胎儿下丘脑-垂体肾上腺轴在启动灵长类动物正常足月分娩和分娩事件中的作用。 该提案汇集了内分泌学和分娩生物学、非人类灵长类动物免疫学和母胎医学方面的专业知识的研究人员，以推进灵长类胎儿主动免疫的使用，以直接解决一个关键问题，即，胎儿 ACTH 调节与非人类灵长类动物分娩相关的肾上腺皮质发育？尽管早产儿的治疗和存活率取得了进步，但美国、加拿大或其他发达国家的早产率（约 9-10%）并未下降。 早产仍然是婴儿死亡的主要原因，并且与神经系统和其他缺陷的风险增加有关。 确定启动正常足月临产和分娩的机制将有助于制定更好的预防早产策略。