Serotonin: budbärare mellan hjärna/tunntarm och skelett. Djurmodeller styrker hypotes om serotoninets roll för bildning av benmassa
Engelsk titel: Serotonin: a messenger between the brain/small intestine and the skeleton. Animal models strengthen the hypothesis about the role of serotonin in bone formation
Läs online
Författare:
Lerner, Ulf H
;
Ohlsson, Claes
;
Ahlman, Håkan
;
Mellström, Dan
Email: ulf.lerner@gu.se
Språk: Swe
Antal referenser: 21
Dokumenttyp:
Översikt
UI-nummer: 11031929
Sammanfattning
Recent studies by Karsenty and co-workers at Columbia University, New York, have demonstrated the importance in skeletal remodeling in mice of serotonin in the brain and in the periphery. Leptin activates receptors in the brain stem which inhibit tryptophane hydroxylase 2 (Tph2), decreasing serotonin biosynthesis. As a consequence, fewer hypothalamic serotonin receptors are activated, sympathetic outflow increases, and there is enhanced activation of ?-adrenergic receptors on osteoblasts. This leads to decreased bone formation, and increased expression of RANKL, which stimulates bone resorption. In contrast, peripheral serotonin is produced in enterochromaffine cells in the dudenum by the enzyme Tph1. Activation of osteoblastic receptors by peripheral serotonin decreases bone formation without affecting RANKL or resorption. Interstingly, pharmacological inhibition of Tph1 in the duodenum can prevent bone loss after ovariectomy in both mice and rats. These preclinical data need to be confirmed in humans and the feedback loops between the skeleton and serontonin releasing cells in brain and gut to be elucidated.