Hypothyroidism and hyperthyroidism modulates Ras-MAPK intracellular pathway in rat thyroids.
Thyrotrophin induces proliferation and function in thyroid cells acting through a seven transmembrane G protein-coupled receptor. The proliferative pathways induced by thyrotropin (TSH) in thyrocytes in vivo are not completely understood yet. The aim of this work is to evaluate if Ras can be induced by TSH in rat thyroids, and whether extracellular regulated kinase (ERK) may be involved in the subsequent intracellular signalling cascade. We induced hypothyroidism in Wistar rats by methimazole (MMI) treatment (0.03% in the drinking water for 21 days). A subset of the hypothyroid rats received T4 (1 microg/100 g bw) during the last 10 days of MMI treatment. Hyperthyroidism was induced by subcutaneous injections of T4 (10 microg/100 g bw) during 10 days in another group of rats. Our data show that in the hypothyroid rats there is a clear positive Ras modulation, but a decrease in pERK. In contrast, thyroidal pERK increases in T4-induced hyperthyroidism, but without any change in RAS, although these changes did not reach statistical significance. Thus, while the rat thyroid proliferation induced by TSH may involve an increase in RAS signalling, the subsequent cascade does not involve ERK phosphorilation, which in fact, increases during T4-induced hyperthyroidism.
Leal
Anna Lúcia R C
AL
Laboratório de Fisiologia Endócrina, Instituto de Biofísica Carlos Chagas Filho, UFRJ, CCS-bloco G, Rio de Janeiro, 21949-900, Brazil.
Pantaleão
Thiago U
TU
Moreira
Débora G
DG
Marassi
Michelle P
MP
Pereira
Valmara S
VS
Rosenthal
Doris
D
Corrêa da Costa
Vânia Maria
VM
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D006980:Hyperthyroidism / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D007037:Hypothyroidism / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D020935:MAP Kinase Signaling System; D008297:Male; D008713:Methimazole; D009929:Organ Size; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D013972:Thyrotropin / Q000097:blood / Q000494:pharmacology; D013974:Thyroxine; D018631:ras Proteins / Q000378:metabolism*
D008713:Methimazole; D013972:Thyrotropin; D018631:ras Proteins; D013974:Thyroxine