The hormonal control of osteoblast activity has been speculated for a long time. In search of such a central hormone, leptin was identified as an inhibitor of bone formation. Intracerebroventricular infusion of leptin resulted in a decrease of bone mass establishing that bone mass is regulated centrally. The peripheral mediator of leptin's action was identified as being the sympathetic nervous system. Mice deficient for catecholamines have high bone mass. beta-receptor agonists decreased bone mass, and conversely, treatment by beta-blockers increased bone mass. (C) 2004 Elsevier Inc. All rights reserved.