RESUMO
The evidence presented here strengthens the argument that RA-induced truncation defects of the embryonic limb, and probably other teratogenic effects, are mediated by the nuclear retinoid receptors, particularly the RAR-beta 2 isoform. Although apoptotic cell death and an increased transglutaminase (tTG) activity accompany teratogenesis, it should be emphasized that the increased levels of RAR-beta 2 may influence additional events in limb development, e.g., modulation of connective tissue differentiation and an inhibition of chondrogenesis. Further work entails screening the effects of RA on genes targeted by the receptors.
Assuntos
Apoptose/efeitos dos fármacos , Deformidades Congênitas dos Membros , Tretinoína/toxicidade , Anormalidades Induzidas por Medicamentos/genética , Anormalidades Induzidas por Medicamentos/metabolismo , Anormalidades Induzidas por Medicamentos/patologia , Animais , Apoptose/genética , Extremidades/embriologia , Extremidades/patologia , Feminino , Troca Materno-Fetal , Mesoderma/efeitos dos fármacos , Mesoderma/patologia , Camundongos , Gravidez , Receptores do Ácido Retinoico/efeitos dos fármacos , Receptores do Ácido Retinoico/genética , Receptores do Ácido Retinoico/metabolismo , Transglutaminases/metabolismoRESUMO
Cultures of cells dissociated from embryonic mouse cerebra were used to demonstrate: (1) that the developmental expression of the mRNA of proteolipid protein is dependent on thyroid hormone; (2) that the expression of the mRNA of proteolipid protein is stimulated not only by triiodothyronine but also by hydrocortisone, which achieve their respective stimulations by an additive and uncompetitive mechanism; (3) the stimulation of the net accumulation of the mRNA of myelin basic protein by hydrocortisone and triiodothyronine is also cooperative, additive, and uncompetitive, and (4) the stimulation of the net accumulation of myelin basic protein, during development by hydrocortisone, is completely dependent on the presence of thyroid hormone. These results suggest that the regulation of the synthesis of myelin basic protein by hydrocortisone requires the presence of triiodothyronine at a posttranscriptional event, but not for transcription itself.