Epigenetic Control of Animal Development - Building the Most Complex Structure on Earth - page 170

Figure 3.40 Diagram of the local sympathetic regulation of bone mass. (A) When leptin
level is low (in nonobese individuals), it does not bind its receptor ObRb in brain stem
neurons, which consequently secrete no serotonin, thus leading to strengthening of the
sympathetic tone (increased noradrenalin secretion). The higher sympathetic tone of the SNS
leads to the inhibition of osteoblast proliferation and increase of osteoclast proliferation,
resulting in bone resorption and bone loss. (B) When leptin level is high (in obese individuals),
it binds its receptors ObRb in brain stem serotonergic neurons, stimulating their electrical
activity, secretion of serotonin, and its binding to Htr2c receptor in specific hypothalamic
neurons. This leads to decreased activity of the sympathetic system (i.e., decreased secretion
of noradrenaline), thus stimulating osteoblast proliferation, with bone growth as a result.
Abbreviations : β2-AR, β2-adrenergic receptor; Htr2c, serotonin receptor; ObRb, leptin
receptor; Per and Cry , period and cryptochrome genes; SNS, sympathetic nervous system;
VMH, ventromedial hypothalamus.
again at work. The organism replaces the lost number of bone cells, so bones remain
in a state of dynamic equilibrium, or homeostasis. Two neural mechanisms for the
maintenance of bone homeostasis are operational in vertebrates: a central and a local
mechanism.
The central neural mechanism of bone homeostasis is very complex and not yet
known in full detail. It responds adaptively to the leptin blood level. When the leptin
level is low, the leptin-sensitive neurons in the brain stem are not activated, and the
hypothalamic VMH (ventromedial nucleus) starts a signal cascade that leads to the
activation of osteoclasts and bone loss ( Figure 3.40 ). When the leptin level is high,
it binds to its receptor ObRb in neurons of the brain stem. These neurons secrete