MECHANISMS OF SKELETAL RECONSTITUTION AFTER LACTATION

繁殖过程中母本的效率对物种繁殖至关重要。哺乳动物骨骼为怀孕期间的胎儿骨骼和哺乳期的产奶量提供矿物质。在生殖周期中，母体骨骼发生了巨大的变化，其中一些可能是为了保护骨骼的完整性。哺乳后的时期是特别“合成代谢”，但机制尚不清楚。为了进一步定义在生殖周期期间和之后发生的母体骨骼适应和机制，提出了以下目标。1）. 确定从妊娠晚期到哺乳期过渡期间骨骼中的细胞和组织事件。我们推测，妊娠后期和哺乳期骨吸收的增加是破骨细胞形成速率增加、寿命延长和细胞凋亡减少的结果。2)确定从哺乳期到断奶后过渡期间骨骼中发生的细胞和组织事件。假设骨形成的增加与成骨细胞形成速率的增加有关但骨吸收的减少是破骨细胞活性降低的结果，形成减少但细胞凋亡增加。3)确定断奶后降钙素（CT）水平升高是否与破骨细胞功能下降相关，并建立泌乳后恢复期的“环境”。我们怀疑与催乳素减少有关，但与雌激素增加和发情开始有关。4)哺乳动物生殖周期中重塑期是否有变化？这将从一个具有皮质内骨重塑的物种的存档材料中确定。5)在哺乳后“恢复”阶段，适度的骨骼负荷是否能改善骨量、结构、强度和动态？我们的假设是，在这一时期，骨骼负荷将对骨骼质量和结构产生协同效应。这些研究将为成年女性骨骼生命中最有活力和“合成代谢”的时期提供新的知识，并可能为生殖能力结束后的疾病治疗提供新的见解。

Maternal efficiency during reproduction is essential for species propagation. The mammalian skeleton provides mineral for the fetal skeleton during pregnancy and milk production during lactation. Dramatic changes occur in the maternal skeleton during the reproductive cycle and some may serve to protect skeletal integrity. The post-lactation period is particularly 'anabolic', but mechanistically not understood. To further define the maternal skeletal adaptations and mechanisms that occur during and after the reproductive cycle, the following aims are proposed. 1). To determine the cellular and tissue events in the skeleton during the transition from late pregnancy to lactation. We hypothesize that the increases in resorption in late pregnancy and sustained during lactation are the result of an increased rate of osteoclast formation, prolongation of lifespan and a decrease in apoptosis. 2) To determine the cellular and tissue events in the skeleton that occur during the transition from lactation to post-weaning. The hypothesis is that increases in bone formation are associated with an increased rate of osteoblast formation but decreased resorption is the result of decreased osteoclast activity, decreased formation but increased apoptosis. 3) To determine if the post-weaning increase in calcitonin (CT) levels is correlated with decreased osteoclastic functions, and establishes the "milieu" for the post-lactational recovery phase. We suspect correlation with decreases in prolactin, but increased estrogen and initiation of estrus. 4) Is there a change in the remodeling period during the reproductive cycle in mammals? This will be determined from archived materials from a species that has intracortical bone remodeling. 5) Does moderate skeletal loading improve bone mass, structure, strength and dynamics during the post-lactation 'recovery' phase? Our hypothesis is that skeletal loading will have synergistic effects on skeletal mass and structure during this period. These studies will provide new knowledge on perhaps the most dynamic and "anabolic" period in the life of the adult female skeleton and may provide new insights into treatments of diseases after reproductive capacity has ended.