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Doctoral Thesis
DOI
10.11606/T.42.2009.tde-06042009-160228
Document
Author
Full name
Luciane Portas Capelo
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2009
Supervisor
Committee
Ferreira, Cecilia Helena de Azevedo Gouveia (President)
Christoffolete, Marcelo Augusto
Maciel, Rui Monteiro de Barros
Silva, Magnus Régios Dias da
Szejnfeld, Vera Lucia
Title in Portuguese
Os hormônios tireoideanos e o desenvolvimento esquelético fetal e pós-natal: estudo do padrão de expressão dos transportadores e das selenodesiodases das iodotironinas.
Keywords in Portuguese
Desenvolvimento ósseo
Hipotireoidismo
Hormônios tireoideanos
Selenodesiodase das iodotironinas do tipo 2
Selenodesiodase das iodotironinas do tipo 3
Transportador de monocarboxílicos
Abstract in Portuguese
Ainda não é claro o papel dos hormônios tireoideanos (HT) no desenvolvimento do esqueleto fetal. Para responder a questão, induzimos hipotireoidismo materno e fetal em camundongos prenhes através da administração de metimazol e perclorato de sódio. O esqueleto fetal apresentou discretas morfológicas até 16,5 dias de idade embrionária (E). Apenas no final da gestação, em 18,5E, foram observadas a redução significativa da zona hipertrófica, do número de condrócitos hipertróficos, desorganização e diminuição da quantidade dos condrócitos proliferativos, além da redução da expressão do colágeno I, X e osteocalcina. Os TRs, assim como LAT1, LAT2 e MCT8 foram detectados em todas as idades estudadas. A alta expressão gênica da D3, principal inativadora do hormônio tireoideano, em 14,5E e sua redução significativa durante o desenvolvimento, até atingir níveis indetectáveis no período pós-natal indicam que a D3 seja responsável por manter baixos níveis de HT no esqueletono início da gestação, garantindo um desenvolvimento ósseo normal.
Title in English
Thyroid hormone and skeletal development at fetal and postnatal ages: the expression pattern of iodothyronine transporters and deiodinases.
Keywords in English
Boné development
Congenital hypothyroidism
Deiodinase type 2
Deiodinase type 3
Monocarboxilate transporter 8
Thyroid hormone
Abstract in English
Thyroid hormone (TH) plays a key role on post-natal bone development and metabolism, while its relevance during fetal bone development is uncertain. To study this, pregnant mice and fetuses were made hypothyroid. The skeleton morphology was preserved up to 16.5 embryonic days (E). Only at E18.5, the hypothyroid fetuses exhibited a reduction in femoral type I and type X collagen and osteocalcin mRNA levels, in the length and area of the proliferative and hypertrofic zones, in the number of chondrocytes per proliferative column, and in the number of hypertrophic chondrocytes. This suggests that up to E16.5, thyroid hormone signaling in bone is kept to a minimum. D3 mRNA was readily detected as early as E14.5 and its expression decreased markedly at E18.5, and even more after birth. The expression levels of D3 gene during early bone development along with the absence of a hypothyroidism-induced bone phenotype at this time suggest that its expression keeps thyroid hormone signaling in bone to very low levels at this early stage of bone development.
 
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Publishing Date
2009-04-07
 
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