PRODUCTION OF NERVE GROWTH-FACTOR BY BROWN FAT IN CULTURE - RELATION WITH THE IN-VIVO DEVELOPMENT STAGE OF THE TISSUE

The regulation of nerve growth factor (NGF) production is still poorly understood. We attempt here to determine whether brown adipose tissue (BAT), which is densely innervated by sympathetic nerve fibres and can be induced to grow in adult rats by simple cold exposure, has the ability to produce NGF and thus to stimulate the growth of its innervation and if so, whether this NGF activity is developmentally regulated. BAT at various stages of development was cocultured with NGF-sensitive sympathetic ganglia in the presence or absence of antiserum to NGF. Both undifferentiated BAT from newborn hamster and differentiated BAT from newborn rat induced neurite outgrowth by producing a neurotrophic factor which was biologically and immunologically indistinguishable from mouse submandibular gland beta (2.5S) NGF. Newborn hamster BAT and BAT from adult rats exposed to cold for 1 or 2 days showed the same high level of NGF activity, whereas the activities of newborn rat BAT, BAT from adult rats at normal room temperature or cold-exposed for 3 days or more were not significantly different from each other and were only about half as high. Newborn hamster BAT and BAT from adult rats cold-exposed for 1 or 2 days are both characterized in vivo by a rapidly increasing mitotic activity of the stromal-vascular cells, which distinguishes them from the other developing tissues tested. Our observations, therefore, suggest a relationship between NGF synthesis and proliferative activity.