MECHANISMS OF SKELETAL RECONSTITUTION AFTER LACTATION

描述（改编自申请人的摘要）： 妊娠期间骨骼代谢的变化（对于胎儿骨骼 矿化）、哺乳期（用于产奶）和断奶后（至 重建矿产储备）。 最近的证据表明 哺乳后骨骼组织的重建（“恢复”）。 的目标 目前提出的研究是，首先，确定的机制， 第二，利用这些信息， 开发骨质减少的范例和策略（例如，绝经后 骨质疏松症）。 具体目标如下：（1）确定 松质骨和皮质骨丢失的“组织水平”机制， 哺乳和哺乳后骨骼恢复。 它是假设 组织水平的建模和重塑机制保护骨骼结构 和功能 不同骨室和包膜的变化将被 在大鼠中使用形态测定法、化学法和吸收测定法测定; 2)确定哺乳期的基本内分泌环境， 哺乳后恢复。 内分泌事件将与 组织水平的骨骼机制; 3）测试假设， 重新建立发情周期对骨骼的保存很重要 在哺乳期和哺乳期后。 建议重新设立 月经周期对人类的恢复很重要，这将是 模拟自然发情启动或延迟（通过诱导 假孕）在大鼠中; 4）测试生理学上 甲状旁腺激素（PTH）短暂升高， 在哺乳期间发生的是合成代谢，而不是分解代谢。 短期 将测量内源性PTH的变化，然后将这些水平 在已知的PTH响应模型中复制以评估合成代谢作用。 （请参阅 申请人建议，这可能是第一次证明， PTH的生理合成代谢作用）;（5）检验假设， 机械负荷是骨骼重建的关键决定因素 哺乳后。 为此，建立了骨架卸载模型， 被利用 总的来说，这些研究旨在提供重要的 关于生命周期中最重要的合成代谢阶段之一的新信息 成年女性的骨骼

DESCRIPTION (Adapted from the Applicant's Abstract): There are substantial changes in skeletal metabolism during pregnancy (for fetal skeletal mineralization), lactation (for milk production), and after weaning (to reconstitute mineral stores). Recent evidence indicates considerable reconstitution of skeletal tissues after lactation ("recovery"). The goals of the presently proposed studies are to, first, determine the mechanisms of this anabolic phase in the female, and, second, to utilize this information to develop paradigms and strategies for osteopenias (e.g., postmenopausal osteoporosis). The following Specific Aims are proposed: 1) to determine the "tissue-level" mechanisms of cancellous and cortical bone loss during lactation and skeletal recovery after lactation. It is hypothesized that tissue-level modeling and remodeling mechanisms protect skeletal structure and function. Changes at different bone compartments and envelopes will be determined using morphometric, chemical and absorptiometric methods in rats; 2) to determine the basic endocrine environment during lactation and recovery after lactation. Endocrine events will be correlated with tissue-level skeletal mechanisms; 3) to test the hypothesis that the re-establishment of an estrus cycle is important in skeletal preservation during and after lactation. It is suggested that re-establishment of the menstrual cycle is important for recovery in the human and this will be modeled with natural estrus initiation or delay (by induction of pseudopregnancy) in rats; 4) to test the hypothesis that physiologically relevant levels of transiently elevated parathyroid hormone (PTH) which occur during lactation are anabolic, rather than catabolic. Shorter-term changes in endogenous PTH will be measured and then these levels will be replicated in a known PTH-responsive model to assess anabolic actions. (The applicant suggests that this could be the first demonstration of a physiologically anabolic role of PTH.); and 5) to test the hypothesis that mechanical loading is a critical determinant of skeletal reconstitution after lactation. For this, an established model of skeletal unloading will be used. Collectively, these studies are intended to provide significant new information on perhaps one of the most anabolic phases in the life-cycle of the adult female skeleton.