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Doctoral Thesis
DOI
10.11606/T.42.2009.tde-25092009-162113
Document
Author
Full name
Tatiana de Lourdes Fonseca
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2009
Supervisor
Committee
Ferreira, Cecilia Helena de Azevedo Gouveia (President)
Boldrini, Sílvia de Campos
Brum, Patricia Chakur
Jorgetti, Vanda
Pereira, Rosa Maria Rodrigues
Title in Portuguese
Interação do sistema nervoso simpático com o hormônio tireoideano na regulação da massa e metabolismo ósseos.
Keywords in Portuguese
Anatomia
Hiperatividade simpática
Hormônio tireoideano
Massa óssea
Metabolismo ósseo
Receptores adrenérgicos
Sistema nervoso simpático
Abstract in Portuguese
Sabe-se que a ativação do Sistema Nervoso Simpático (SNS) induz osteopenia via adrenoceptores b2 (b2-AR). Para investigar se o hormônio tireoideano (HT) interage com o SNS para regular a massa óssea, estudamos o efeito do HT em associação com isoproterenol ou propranolol (agonista e antagonista b-adrenérgicos) e avaliamos o efeito do HT em camundongos com elevado tônus simpático, devido à dupla inativação gênica do a2A-AR e a2C-AR (a2A/a2C-AR-/-), autorreceptores que inibem a liberação de noradrenalina. Vimos que esses animais apresentam um fenótipo de alta massa óssea, apesar do elevado tônus simpático e de intacta sinalização b2-adrenérgica, sugerindo que o a2A-AR e/ou a2C-AR, além do b2-AR, possam mediar ações do SNS no osso. O propranolol limitou e o isoproterenol acentuou os efeitos deletérios do HT no esqueleto, já os animais a2A/a2C-AR-/- apresentaram resistência à osteopenia induzida pela tireotoxicose, o que sugere que há interação entre SNS e o HT para regular a massa óssea, e que esta depende tanto do b2-AR como do a2A- e/ou a2C-AR.
Title in English
Interaction of the sympathetic nervous system with thyroid hormone in the regulation of bone mass and metabolism.
Keywords in English
Adrenergic receptors
Anatomy
Bone mass
Bone metabolism
Sympathetic hyperactivity
Sympathetic nervous system
Thyroid hormone
Abstract in English
It is known that the sympathetic nervous system (SNS) activation induces ostepenia, via b2-adrenoceptors (b2AR). To investigate if thyroid hormone (TH) interacts with the SNS to regulate bone mass, we studied the effect of TH in association with isoproterenol or propranolol (b-adrenergic agonist and antagonist) and evaluated the effect of TH in mice with a chronic elevated sympathetic tone, due to double disruption of a2A-AR and a2C-AR (a2a/a2c-AR-/-), autoreceptors that inhibit noradrenalin release. We showed that KO mice present a high bone mass phenotype in spite of an elevated sympathetic tone and of intact b2-adrenergic signaling, which suggests that a2A- and/or a2C-AR, besides b2-AR, may also mediate the SNS actions in the bone. Propranolol limited and isoproterenol accentuated the deleterious effects of TH in the skeleton, while a2A/a2C-AR-/- mice presented resistance to the T3-induced osteopenia, which suggest that there is an interaction between the SNS and TH to regulate bone mass, and that it is dependent on b2-AR and a2A-AR and/or a2C-AR signaling.
 
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Publishing Date
2010-03-26
 
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