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Biphasic modulation of insulin receptor substrate-1 during goitrogenesis
Grozovsky, R; Morales, M. M; Carvalho, D. P.
  • Grozovsky, R; Universidade Federal do Rio de Janeiro. Laboratório de Fisiologia Endócrina. Rio de Janeiro. BR
  • Morales, M. M; Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Fisiologia Celular e Molecular. Rio de Janeiro. BR
  • Carvalho, D. P; Universidade Federal do Rio de Janeiro. Laboratório de Fisiologia Endócrina. Rio de Janeiro. BR
Braz. j. med. biol. res ; 40(5): 679-686, May 2007. ilus, graf, tab
Article in English | LILACS | ID: lil-449077
ABSTRACT
Insulin receptor substrate-1 (IRS-1) is the main intracellular substrate for both insulin and insulin-like growth factor I (IGF-I) receptors and is critical for cell mitogenesis. Thyrotropin is able to induce thyroid cell proliferation through the cyclic AMP intracellular cascade; however, the presence of either insulin or IGF-I is required for the mitogenic effect of thyroid-stimulating hormone (TSH) to occur. The aim of the present study was to determine whether thyroid IRS-1 content is modulated by TSH in vivo. Strikingly, hypothyroid goitrous rats, which have chronically high serum TSH levels (control, C = 2.31 ± 0.28; methimazole (MMI) 21d = 51.02 ± 6.02 ng/mL, N = 12 rats), when treated with 0.03 percent MMI in drinking water for 21 days, showed significantly reduced thyroid IRS-1 mRNA content. Since goiter was already established in these animals by MMI for 21 days, we also evaluated IRS-1 expression during goitrogenesis. Animals treated with MMI for different periods of time showed a progressive increase in thyroid weight (C = 22.18 ± 1.21; MMI 5d = 32.83 ± 1.48; MMI 7d = 31.1 ± 3.25; MMI 10d = 33.8 ± 1.25; MMI 14d = 45.5 ± 2.56; MMI 18d = 53.0 ± 3.01; MMI 21d = 61.9 ± 3.92 mg, N = 9-15 animals per group) and serum TSH levels (C = 1.57 ± 0.2; MMI 5d = 9.95 ± 0.74; MMI 7d = 10.38 ± 0.84; MMI 10d = 17.72 ± 1.47; MMI 14d = 25.65 ± 1.23; MMI 18d = 35.38 ± 3.69; MMI 21d = 31.3 ± 2.7 ng/mL, N = 9-15 animals per group). Thyroid IRS-1 mRNA expression increased progressively during goitrogenesis, being significantly higher by the 14th day of MMI treatment, and then started to decline, reaching the lowest values by the 21st day, when a significant reduction was detected. In the liver of these animals, however, a significant decrease of IRS-1 mRNA was detected after 14 days of MMI treatment, a mechanism probably involved in the insulin resistance that occurs in hypothyroidism. The increase in IRS-1 expression during goitrogenesis may represent...
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Full text: Available Index: LILACS (Americas) Main subject: Thyroid Gland / Thyrotropin / Adaptor Proteins, Signal Transducing / Goiter / Hypothyroidism Limits: Animals Language: English Journal: Braz. j. med. biol. res Journal subject: Biology / Medicine Year: 2007 Type: Article / Project document Affiliation country: Brazil Institution/Affiliation country: Universidade Federal do Rio de Janeiro/BR

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Full text: Available Index: LILACS (Americas) Main subject: Thyroid Gland / Thyrotropin / Adaptor Proteins, Signal Transducing / Goiter / Hypothyroidism Limits: Animals Language: English Journal: Braz. j. med. biol. res Journal subject: Biology / Medicine Year: 2007 Type: Article / Project document Affiliation country: Brazil Institution/Affiliation country: Universidade Federal do Rio de Janeiro/BR