IMMUNIZATION AGAINST ACTH AND PARTURITION

针对 ACTH 和分娩的免疫接种

• 批准号: 6197475
• 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 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6197475
• 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.

该提议的目的是直接对狒狒胎儿对肾上腺皮质激素（ACTH）进行免疫免疫，并确定ACTH免疫中性化对两种胎儿肾上腺皮质功能的影响（脱氢性性皮层硫酸硫酸盐[DHEAS]和皮质溶液的合成）和牙齿长度。 灵长类动物肾脏肾上腺皮质是雌激素的雄激素的重要来源。 雌激素的产生是调节导致灵长类动物出生的分子和生物物理级联的不可或缺的一部分。 尽管灵长类动物胎儿肾上腺是雌激素形成的雄激素前体的重要性，但灵长类动物胎儿在分娩过程中的作用仍未解决。我们建议在灵长类动物胎儿中积极免疫胎儿狒狒对ACTH，主要调节皮质醇和DHEA产生的主要肽。 主动免疫已被用作研究内源性肽和蛋白质激素在各种物种成年人中的作用。 子宫内狒狒胎儿的免疫提供了一种优雅的方法，可以批判性地检查胎儿下丘脑垂体肾上腺轴在启动正常术语劳动和在灵长类动物中分娩的事件中的作用。 该提案汇集了研究人员在分泌和生物学，非人类灵长类动物的免疫学和孕产妇胎儿医学方面具有专业知识的研究，以促进灵长类动物胎儿的主动免疫的使用直接解决关键问题，即胎儿ACTH在调节与非人类灵长类动物的分娩有关的肾上腺皮质发展中？尽管在早产儿的治疗和存活率方面取得了进步，但在美国，加拿大或其他发达国家，早产率（约9-10％）的患病率尚未下降。 早产仍然是婴儿死亡率的主要原因，并且与神经系统和其他缺陷的风险增加有关。 确定启动正常劳动和分娩发作的机制将导致制定更好的策略以防止早产。