Issue |
Med Sci (Paris)
Volume 17, Number 12, Décembre 2001
|
|
---|---|---|
Page(s) | 1270 - 1275 | |
Section | Articles de Synthèse | |
DOI | https://doi.org/10.1051/medsci/200117121270 | |
Published online | 15 December 2001 |
Contrôle central de la formation osseuse
Leptin controls bone formation through a hypothalamic relay
Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Place, Houston TX 77030, États-Unis
L’observation que l’arrêt des fonctions gonadiques favorise l’apparition de l’ostéoporose alors que l’obésité prévient la perte osseuse nous a amenés à postuler que la masse osseuse, les fonctions gonadiques et la reproduction sont contrôlées par les mêmes hormones. Une analyse in vivo utilisant des méthodes génétiques et physiologiques a permis de démontrer que la leptine est le plus puissant inhibiteur de la formation osseuse identifié à ce jour. Les mêmes études in vivo ont permis de démontrer également que cette fonction de la leptine, comme les autres, requiert sa liaison à un récepteur hypothalamique. Cette étude démontre que, comme la plupart des autres fonctions homéostatiques, le remodelage osseux est sous le contrôle de l’hypothalamus. Cette étude suggère aussi que les maladies osseuses dégénératives telle que l’ostéoporose pourraient être en partie d’origine hypothalamique.
Abstract
Menopause favors osteoporosis and obesity protects from it. In an attempt to decipher the molecular bases of these two well known clinical observations, we hypothesized that they meant that bone remodeling, body weight, and reproduction are controlled by identical endocrine pathways. We used mouse genetics as a tool to translate these clinical observations into a molecular hypothesis. The ob/ob and db/db mice were valuable models, since two of the three functions thought to be co-regulated are affected in these mice : they are obese and hypogonadic. Surprisingly, given their hypogonadism, both mouse mutant strains have a high bone mass phenotype. Subsequent analysis of the mechanism leading to this high bone mass revealed that this was due to an increase of bone formation. All data collected indicate that, in vivo, leptin does not act directly on osteoblasts but rather through a central pathway following binding to its specific receptors located on hypothalamic nuclei. This result revealed that bone remodeling, like most other homeostatic functions, is under a hypothalamic control. The nature of the signal downstream of the hypothalamus is unknown for now but current experiments are attempting to identify it.
© 2001 médecine/sciences - Inserm / SRMS
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