Avaliação da relação dos níveis séricos do hormônio do crescimento e genótipo GHRD3 com a expressão do receptor do hormônio do crescimento, número de neurofibromas e macrocefalia na neurofribomatose tipo 1

• Autor(a) principal: Andrade, Raquel Machado
• Data de Publicação: 2013
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da Universidade Federal Fluminense (RIUFF)
• Texto Completo: https://app.uff.br/riuff/handle/1/20227
• topic: Neurofibromatose tipo 1; Neurofibromas; Macrocefalia; Receptores do hormônio do crescimento; Polimorfismo genético; MEDICINA; PATOLOGIA; Hormônio do crescimento; Macrocefalia; Type 1 neurofibromatosis; Neurofibromas; Macrocephaly; Growth hormone receptor; Polymorphism genetics; CNPQ::CIENCIAS DA SAUDE::MEDICINA::ANATOMIA PATOLOGICA E PATOLOGIA CLINICA

Introduction: Neurofibromatosis type 1 (NF1), it is believed that hormonal factors are important in the pathogenesis of neurofibromas. Most neurofibromas express the growth hormone receptor (GHR), however it is unclear whether there is any relation between this expression with serum levels of growth hormone (GH), GH is neurofibromas produce and if there is a relationship between the number of neurofibromas as well as height and macrocephaly, with the deletion polymorphism in exon 3 of the GHR gene (GHRd3), which is believed to be associated with increased responsiveness to GH. General Objective: To investigate the expression of growth hormone and its receptor in neurofibromas of patients with neurofibromatosis type 1 and evaluate the relationship of serum growth hormone and genotype GHRd3 with number of neurofibromas, receptor expression of growth hormone in these tumors and macrocephaly. Methods: We evaluated 67 individuals with NF1 in relation to height, head circumference and total number of cutaneous neurofibromas / subcutaneous, being quantified and classified. The sample contained 100 neurofibromas neurofibromas of subjects of care and more than 41 individuals with NF1 and 13 individuals without NF1 obtained the file from the Department of Pathology, University Hospital Antonio Pedro. We assessed the expression of GHR in neurofibormas by immunohistochemistry, using the technique of tissue micro and macroarray, antibodies and anti-GHR-GH. The cases was performed using the computerized system of Aperio ePathology Solutions. GHRd3 polymorphism was evaluated by polymerase chain reaction (PCR) multiplex. Measurement of serum GH assay was performed imunoabsorbância. Results: The polimofismo GHRd3 was not related to the amount and size of neurofibromas, the GHR expression in neurofibromas, serum GH and macrocephaly of individuals with NF1. The GHR expression was observed in 98.5% of patients with NF1 neurofibromas and 100% of neurofibromas not associated with the syndrome. There was no expression of GH in any of the studied neurofibromas and serum hormone did not own relationship with the number and size of tumors, expression of GHR and stature and macrocephaly. It was observed that tumors over expressing GHR more than smaller tumors. Conclusion: The majority of neurofibromas, independent association with NF1, expresses the growth hormone receptor in similar amounts. Mast cells in most neurofibromas express the receptor of growth hormone. Neurofibromas do not express hormone crescimento.Quanto largest neurofibroma, the greater the receptor expression of growth hormone. The expression of growth hormone receptor in neurofibromas has no relation to genotype GHRd3, nor with serum levels of growth hormone in individuals with NF1. The expression of growth hormone receptor in neurofibromas no different at different ages in individuals with NF1. Most individuals with NF1 has short stature and macrocephaly, and macrocephaly more common in women. These characteristics, as well as the number of neurofibromas and genotype GHRd3 not seem to be related to serum levels of GH. GHRd3 polymorphism has no impact on the number of neurofibromas and macrocephaly in individuals with NF1