Osteoblasts are a new target for prolactin: Analysis of bone formation in prolactin receptor knockout mice

Bone development is a multistep process that includes patterning of skeleta l elements. commitment of hematopoietic and/or mesenchymental cells to chon drogenic and osteogenic lineages, and further differentiation into three sp ecialized cell types: chondrocytes in cartilage and osteoblasts and osteocl asts in bone. Although PRL has a multitude of biological actions in additio n to its role in the mammary gland, very little is known about its effect o n bone. Mice carrying a germline null mutation for the PRL receptor gene ha ve been produced in our laboratory and used to study the role of PRL in bon e formation. In -/- embryos, we observed an alteration in bone development of calvaria. In adults, histomorphometric analysis showed that the absence of PRL receptors leads to a decrease in bone formation rate using double ca lcein labeling and a reduction of bone mineral density, measured by dual en ergy x-ray absorptiometry. In addition, serum estradiol, progesterone, test osterone, and PTH levels were analyzed. We also established that osteoblast s, but not osteoclasts, express PRL receptors. This suggests that an effect of PRL on osteoblasts could be required for normal bone formation and main tenance of bone mass. Thus, the PRL receptor knockout mouse model provides a new tool to investigate the involvement of PRL in bone metabolism.