Alterations in Dexras1 expression mediated by STAT5 and GR cross-talk contribute to the modulation of insulin secretion during pregnancy and lactation. / Alterações na expressão de Dexras1 mediada pela cooperação entre STAT5 e GR contribuem para modulação da secreção de insulina na gestação e lactação.
AUTOR(ES)
Camilo de Lellis Santos
DATA DE PUBLICAÇÃO
2010
RESUMO
It is not clear how glucocorticoid receptor (GR) counteracts STAT5 activity during the transition of pregnancy to lactation. Dexras1 is a small G protein activated by dexamethasone (DEX) that controls cell morphology, growth, etc. In the present study we detected Dexras1 expression in pancreatic beta cell. DEX induces Dexras1 expression in RINm5F cells, which is increased in pregnancy and decreased in lactation. The expression of 11βHSD1, the glucocorticoids (GCs) activating enzyme, followed Dexras1 profile in pancreatic islet. Both GR and STAT5b bindings to Dexras1 gene promoter, analyzed by ChIP assay, are increased by DEX and PRL counteracts this effect. Both bindings are decreased in pregnancy and increased in lactation. DEX induces STAT5b association to GR, phosphorylation and nuclear translocation. Dexras1 knockdown using small interference RNA (si-RNA) promoted an increase in insulin secretion, as well as increased levels of pERK1/2, pCREB, pPKCδ and PKA. Thus, Dexras1 regulation by PRL and GCs contributes to insulin secretion during peripartum.
ASSUNTO(S)
lactação pancreatic islets lactation dexras1 prolactin gravidez glicocorticóides dexras1 prolactina glucocorticoids ilhotas pancreáticas pregnancy
