IMMUNIZATION AGAINST ACTH AND PARTURITION

本建议的目的是直接，主动免疫狒狒胎儿对促肾上腺皮质激素（ACTH），并确定胎儿肾上腺皮质功能（硫酸脱氢表雄酮[DHEAS]和皮质醇合成）和妊娠期的长度的免疫中和ACTH的效果。 灵长类胎儿肾上腺皮质是胎盘芳构化为雌激素的雄激素的重要来源。 雌激素的产生是调节灵长类动物出生的分子和生物物理级联的组成部分。 尽管灵长类胎儿肾上腺作为雌激素形成的雄激素前体来源的重要性，灵长类胎儿在分娩过程中的作用仍然没有得到解决。我们建议积极免疫胎儿狒狒对促肾上腺皮质激素，主要肽调节皮质醇和脱氢表雄酮生产的灵长类动物胎儿。 主动免疫已被用作检查内源性肽和蛋白质激素在各种物种的成虫中的作用的技术。 狒狒胎儿在子宫内的免疫接种提供了一种优雅的方法来严格检查胎儿下丘脑-垂体肾上腺轴在灵长类动物正常足月分娩和分娩事件中的作用。 这项建议汇集了研究人员的专业知识，内分泌学和分娩生物学，免疫学的非人灵长类动物，和母胎医学，以促进使用主动免疫的灵长类动物胎儿直接解决一个关键问题，即胎儿ACTH在调节肾上腺皮质发育的作用与分娩在非人灵长类动物？虽然在早产儿的治疗和存活率方面取得了进展，但在美国、加拿大或其他发达国家，早产的患病率（约9- 10%）并没有下降。 早产仍然是婴儿死亡的主要原因，并与神经和其他缺陷的风险增加有关。 确定启动正常足月分娩和分娩的机制将有助于制定更好的预防早产的策略。

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.