Assuntos
Sistema Nervoso Central/fisiologia , Fator de Crescimento Insulin-Like I/farmacologia , Fator de Crescimento Insulin-Like I/fisiologia , Neurônios/fisiologia , Oligopeptídeos/farmacologia , Receptor IGF Tipo 1/metabolismo , Sequência de Aminoácidos , Animais , Ligação Competitiva , Sistema Nervoso Central/efeitos dos fármacos , Humanos , Fator de Crescimento Insulin-Like I/química , Modelos Neurológicos , Dados de Sequência Molecular , Neurônios/efeitos dos fármacos , Estrutura Secundária de ProteínaRESUMO
Insulin-like growth factor 1 (IGF-1) is involved in the regulation of brain development and has been suggested as an autocrine stimulator of brain tumor cell proliferation. This study demonstrates the expression of IGF-1 in tumor tissue from human gliomas and one esthesioneuroblastoma. Using immunohistochemistry, expression of an IGF-1-like peptide was localized in tumor cells of 6 of the 9 gliomas examined as well as the esthesioneuroblastoma. From one anaplastic oligodendroglioma (which showed strong IGF-1 immunostaining) the IGF-1 transcripts were characterized after isolation of mRNA followed by amplification using the reverse transcriptase-polymerase chain reaction. Two IGF-1 complementary DNAs resulting from alternative splicing of the IGF-1 primary transcript were identified. These transcripts encode two different precursor proteins which correspond to Ea IGF-1 and Eb IGF-1. The significance of IGF-1 alternative mRNA splicing pathways remains to be determined.
Assuntos
Neoplasias Encefálicas/química , Glioma/química , Fator de Crescimento Insulin-Like I/análise , Tumores Neuroectodérmicos Primitivos Periféricos/química , RNA Mensageiro/análise , RNA Neoplásico/análise , Sequência de Aminoácidos , Sequência de Bases , Humanos , Fator de Crescimento Insulin-Like I/química , Dados de Sequência Molecular , RNA Mensageiro/química , RNA Neoplásico/químicaRESUMO
Insulin-like growth factor 1 (IGF-1) regulates growth of the brain. In order to characterize the variant IGF-1 present in human fetal brain we have determined the cDNA sequence for human fetal brain IGF-1. Using PCR to amplify cDNA obtained from isolated human fetal brain mRNA, two cDNA sequences encoding precursor proteins which correspond to IGF-1a and IGF-1b were obtained. This is the first characterisation of IGF-1 and its IGF-1a and IGF-1b precursors in the nervous system.
Assuntos
Córtex Cerebral/fisiologia , DNA/genética , Fator de Crescimento Insulin-Like I/genética , Sequência de Aminoácidos , Sequência de Bases , Córtex Cerebral/embriologia , Feto , Idade Gestacional , Humanos , Dados de Sequência Molecular , Poli A/genética , Poli A/isolamento & purificação , RNA/genética , RNA/isolamento & purificação , RNA Mensageiro , Homologia de Sequência do Ácido NucleicoRESUMO
Insulin-like growth factors (IGF-I and -II) are present in the brain during development, with high levels of both being also found in the periphery particularly in the embryo. IGFs in the brain are believed to stimulate the proliferation of neuronal and glial precursors and their phenotypic differentiation. Using in situ hybridization, we have investigated the distribution of cells producing IGF-I and -II in the rat fetus during the second half of prenatal development with special emphasis on the peripheral and central nervous system. High levels of IGF-I mRNA were found in the olfactory bulb and in discrete neurons of the cranial sensory ganglia, notably in the trigeminal ganglion, as early as 13 days of gestation, in the pineal primordium of 18 day old fetuses, and in discrete groups of cells in the cochlear epithelium located laterally outside the forming spiral organ, in day 13 to 21 fetuses. High levels of IGF-II mRNA in the brain, besides the choroid plexus and the leptomeninges, were detected in hypothalamus, in the floor of the 3rd ventricle at all stages studied, in the pineal primordium at 18 days and in the pars intermedia of the pituitary or in the Rathke's pouch epithelium from which it is derived, with progressive fading towards the end of the gestation. In the peripheral nervous system the IGF-II mRNA was only found in association with the vascular endothelia of the ganglia. IGF-II mRNA in the nervous system was found in highly vascularized areas, meninges, blood vessels and choroid plexuses. It is thus associated with structures involved in the production of extracellular fluids and/or substrate transport and supply in the nervous tissues. A more specific role in the differentiation or fetal endocrine function should be considered for IGF-II in cells producing melatonin and melanocyte stimulating hormone (MSH) in the pineal and pituitary glands, respectively. The presence of IGF-I mRNA in the nervous system could be associated with fiber outgrowth and synaptogenesis in the cases of olfactory bulb and developing iris. The role of IGF-I in restricted populations of cells of the cochlear epithelium and in the pineal gland is unclear and requires further investigations including a search for IGF-I receptors in possible target cells. In the sensory ganglia, the presence of high levels of IGF-I mRNA eventually corresponds to the production, by post-translational processing, of the amino-terminal tripeptide of IGF-I, which might represent a neurotransmitter for these sensory neurons.
