MECHANISMS OF SKELETAL RECONSTITUTION AFTER LACTATION
Principal Investigator: Scott Miller
Abstract: 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.
Funding Period: 1998-08-01 - 2006-07-31
more information: NIH RePORT
- Weaning initiates a rapid and powerful anabolic phase in the rat maternal skeletonScott C Miller
Division of Radiobiology, Department of Radiology, School of Medicine, University of Utah, Salt Lake City, 84108, USA
Biol Reprod 73:156-62. 2005..Many, if not most of these newly formed osteoblasts were derived from proliferating progenitors. It is possible that the endocrine milieu of lactation expands or primes the osteoprogenitor pool for this rapid anabolic phase...
- Rapid inactivation and apoptosis of osteoclasts in the maternal skeleton during the bone remodeling reversal at the end of lactationScott C Miller
Division of Radiobiology, Department of Radiology, School of Medicine, University of Utah, Salt Lake City, Utah 84108, USA
Anat Rec (Hoboken) 290:65-73. 2007..These results also suggest that bone remodeling is well synchronized prior to, during, and after lactation to accommodate the mineral requirements of the offspring as well as the mother...