[Bone mass regulation by leptin: a hypothalamic control of bone formation].
Bone mass is maintained constant between puberty and menopause by the balance between osteoblasts and osteoclasts activity. The existence of a hormonal control of osteoblast activity has been speculated for years by analogy to osteoclast biology. Through the search for such humoral signal(s) regulating bone formation, leptin has been identified as a powerful inhibitor of bone formation. Furthermore, by means of intracerebroventricular infusion of leptin, it has been shown that the effect of this adipocyte-derived hormone on bone is mediated via a brain relay, like all its other functions. Subsequent studies have led to the identification of hypothalamic neurons involved in leptin's antiosteogenic function. In addition, it has been shown that those neurons or neuronal pathways are distinct from neurons responsible for the regulation of energy metabolism. Finally, the peripheral mediator of leptin's antiosteogenic function has been identified as being the sympathetic nervous system. Catecholamine-deficient mice have a high bone mass and sympathomimetics administered to mice decreased bone formation and bone mass. Conversely, beta-blockers increased bone formation and bone mass and blunt the bone loss induced by ovariectomy.
Elefteriou
F
F
Département de génétique moléculaire et humaine, Bone disease program of Texas, Baylor College of Medicine, Houston, 77030 Texas, Etats-Unis.
Karsenty
G
G
D017667:Adipocytes / Q000378:metabolism; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001835:Body Weight; D001846:Bone Development / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate; D020738:Leptin / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D008820:Mice, Obese; D009474:Neurons / Q000502:physiology; D009765:Obesity / Q000503:physiopathology; D009929:Organ Size; D010006:Osteoblasts / Q000502:physiology*; D015663:Osteoporosis, Postmenopausal / Q000503:physiopathology; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D054411:Receptors, Leptin; D013564:Sympathetic Nervous System / Q000502:physiology; D014697:Ventromedial Hypothalamic Nucleus / Q000187:drug effects / Q000502:physiology*
D000319:Adrenergic beta-Antagonists; C515448:LEPR protein, human; D020738:Leptin; D011943:Receptors, Adrenergic, beta; D054411:Receptors, Leptin; C515447:leptin receptor, mouse