RESUMO
Sirtuins 1-7 (SIRT) are a highly conserved family of histone deacetylases involved in the regulation of longevity that have a considerable impact in transcription, DNA repair regulation, telomeric stability, cell senescence and apoptosis. In the present study, SIRT1-7 mRNA levels were evaluated in 37 somatotropinomas and 31 nonfunctioning pituitary adenomas (NFPAs) using qPCR and relation to tumor size, invasiveness and Ki-67 proliferative index was made. Overexpression of SIRT1 was observed in 86.5% of somatotropinomas versus 41.9% of NFPAs (P < 0.01). SIRT3 was more underexpressed in NFPAs than somatotropinomas (77.4 and 40.5%, respectively, P < 0.01) as well as SIRT4 and SIRT7. Despite the lack of association between sirtuins and invasiveness or Ki-67 index, SIRT1 and SIRT3 expressions were related to tumor size. Mean of the largest diameter was smaller in adenomas with SIRT1 overexpression than with normal expression (P < 0.01) and SIRT3 underexpression was associated with larger tumors (P < 0.01). In conclusion, a pronounced difference in sirtuins expression was identified between pituitary adenomas, suggesting that these genes are potential markers of pituitary adenomas and could be employed in the characterization of somatotropinomas and NFPAs. The role of sirtuins in pathogenesis of pituitary tumors merits further investigation and possibly will provide new molecular insight about their progression.
Assuntos
Adenoma/metabolismo , Neoplasias Hipofisárias/metabolismo , Sirtuínas/metabolismo , Adenoma/genética , Adenoma/patologia , Adulto , Feminino , Adenoma Hipofisário Secretor de Hormônio do Crescimento/genética , Adenoma Hipofisário Secretor de Hormônio do Crescimento/metabolismo , Adenoma Hipofisário Secretor de Hormônio do Crescimento/patologia , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/patologia , Sirtuína 1/genética , Sirtuína 1/metabolismo , Sirtuína 2/genética , Sirtuína 2/metabolismo , Sirtuína 3/genética , Sirtuína 3/metabolismo , Sirtuínas/genéticaRESUMO
We describe a patient with severe muscle cytochrome c oxidase deficiency who had de Toni-Fanconi-Debré syndrome and acute neurologic deterioration resembling Leigh syndrome, without clear evidence of muscle abnormality. Metabolic investigations revealed elevated cerebrospinal fluid lactate values contrasting with normal blood lactate, and high 3-hydroxybutyrate/acetoacetate ratio with normal lactate/pyruvate ratio. This case emphasizes the importance of performing metabolic and biochemical investigations in every patient with Leigh syndrome, even in the absence of hyperlactatemia or myopathy.