PARTURITION AND FETAL PRIMATE HYPOTHALAMIC FUNCTION

简介：在项目I中，在PO 1 6-10年期间，我们扩大了我们的狒狒 研究，使长期胎儿导管插入术，以回答关键 运动和胎儿的问题。我们现在将重点关注 胎儿下丘脑-垂体-肾上腺-胎盘环（HPAPL） 妊娠狒狒和胎儿，并确定关键的调节机制 我们在第6 - 10年研究的雌激素的变化。 假设：我们提出四个假设，有四个相关的具体目标： 1.增加活动的胎儿狒狒HPAPL发生在足月， 类似的方式是平行的，类似于既定的模式， 垂体肾上腺活动被证明是中枢启动 羊的分娩 2.母体CRH在调节a）子宫血液中起内分泌作用 血流，B）子宫肌层活动和c）妊娠持续时间。 3.在妊娠0.7至 通过单独输注PGHS 1和PGHS 2抑制剂或同时输注 将改变材料和胎儿HPAPL功能和子宫肌层活性。 4.将有妊娠和分娩相关的变化， 刺激性和抑制性PG的比例、位置和受体类型 和CRH受体以及子宫肌层和蜕膜中PGHS和CRH的产生。 方法：我们将使用长期仪器的母亲和胎儿狒狒 从122 dGA到足月（175 dGA）。我们将通过以下方式实现我们的具体目标： 纵向取样：2）使用CRH，一种生物中和抗CRH抗体; 3)使用不同的PH合成抑制剂和4）与一个完整的范围， PH和CRH受体的探针。 依据：大多数控制母体和胎仔的长期体内研究 已在绵羊中进行HPAPL、分娩和子宫肌层功能。 在非人类灵长类动物中进行的长期研究很少。 胎儿和母体内分泌和子宫肌层的差异 绵羊和灵长类动物之间的收缩性决定了 对人类分娩控制的理解还有待实验证实 数据来自非人类灵长类动物。 分娩是一个多因素的过程，有相互关联的正反馈- 正向和负反馈回路。项目I与项目II相互作用 和III，以实现基础胎儿和 母体神经内分泌机制和分娩。预防和 早产和早产的管理是关键问题， 人类产科学，两者都需要更好地了解这一过程， 我们建议在这个重要的非人类灵长类动物模型中进行研究。

INTRODUCTION: In Project I during PO1 years 6-10 we expanded our baboon studies to enable chronic fetal catheterizations to answer critical questions in both motor and fetus. We will now focus on regulation of fetal hypothalamic-pituitary-adrenal-placental loops (HPAPL) in the pregnant baboon and fetus and determine the critical regulatory mechanisms that drive the changes in estrogen that we studied in years 6 - 10. HYPOTHESES: We propose four hypotheses with four related specific aims: 1. Increased activity of the fetal baboon HPAPL occurs at term in a fashion that parallels and is analogous to the well established pattern in pituitary adrenal activity demonstrated to be central to the initiation of parturition in sheep. 2. Maternal CRH plays an endocrine role in regulating a) uterine blood flow, b) myometrial activity and c) duration of pregnancy. 3. Inhibition of prostaglandin (PG) synthesis between 0.7 of gestation and term by infusion of PGHS1 and PGHS2 inhibitors independents or together will alter material and fetal HPAPL function and myometrial activity. 4. There will be gestation and parturition related changes in the proportion, position, and receptor-type of stimulatory and inhibitor PG and CRH receptors and PGHS and CRH production in myometrium and decidua. Methods: We will use chronically instrumented maternal and fetal baboons from 122 dGA to term (175 dGA). We will address our Specific Aims 1) by longitudinal sampling: 2) using CRH, a bioneutralizing anti-CRH antibody; 3) using different PH synthesis inhibitors and 4) with a complete range of probes for PH and CRH receptors. RATIONALE: Most chronic in vivo studies on control of maternal and fetal HPAPL, parturition, and myometrial function have been performed in sheep. Studies in chronically instrumented non-human primates are few. Differences in fetal and maternal endocrinology and myometrial contractility between sheep and primates dictate that a clear understanding of control of human parturition awaits firm experimental data from non-human primates. Labor is a multi-factorial process with interconnected positive feed- forward and negative feedback loops. Project I interacts with Projects II and III to enable cross-species comparison of fundamental fetal and maternal neuroendocrine mechanisms and parturition. Prevention and management of pre-term labor and pre-term birth are critical issues in human obstetrics and both require a better understanding of the processes we propose to study in this important non-human primate model.