MECHANISMS OF SKELETAL RECONSTITUTION AFTER LACTATION

描述(改编自申请人的摘要)：有大量 怀孕期间骨骼代谢的变化(对于胎儿骨骼 矿化)、哺乳(用于产奶)和断奶后(至 重组矿物库)。最近的证据表明有相当大的 哺乳后骨骼组织的重建(“恢复”)。目标 目前提议的研究的一部分是，首先确定 女性的这一合成代谢阶段，第二，利用这一信息 为骨质疏松症(如绝经后)制定范例和策略 骨质疏松)。提出了以下具体目标：1)确定 骨松质和皮质骨丢失的“组织水平”机制 哺乳和哺乳后骨骼恢复。据推测， 组织级建模和重塑机制保护骨骼结构 和功能。不同骨骼隔间和封套上的更改将是 采用形态计量学、化学计量学和吸光度计量学方法对大鼠进行测定； 2)测定哺乳期和哺乳期基本内分泌环境 哺乳后恢复正常。内分泌事件将与 组织水平的骨骼机制；3)测试假设 重建发情周期在骨骼保存中很重要 哺乳期间和哺乳后。有人建议，重新设立 月经周期对人类的恢复很重要，这将是 以自然发情开始或延迟(通过诱导 假孕)；4)检验生理学假说 短暂升高的甲状旁腺激素(PTH)相关水平 发生在哺乳期的是合成代谢，而不是分解代谢。较短期的 将测量内源性甲状旁腺素的变化，然后这些水平将被 在已知的甲状旁腺素反应模型中复制以评估合成代谢作用。( 申请人表示，这可能是第一次展示 PTH在生理上的合成代谢作用)；以及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，已建立的骨骼卸载模型将 被利用。总而言之，这些研究旨在提供有意义的 关于生命周期中可能是最合成代谢的阶段之一的新信息 成年女性的骨架。

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.