Laboratorio de Endocrinologia Celular e Molecular, LIM25, Disciplina de Endocrinologia, Hospital das Clinicas, FMUSP, Rua Dr Arnaldo, 455 -LIM25, 4o andar, sala 4305, Cerqueira César, Sao Paulo, SP, CEP 01246-903, Brazil.
Unidade de Neuroendocrinologia, Disciplina de Endocrinologia, Hospital das Clinicas, FMUSP, Sao Paulo, Brazil.
Pituitary. 2018 Aug;21(4):355-361. doi: 10.1007/s11102-018-0881-7.
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.
Sirtuins 1-7（SIRT）是一组高度保守的组蛋白去乙酰化酶家族，参与长寿的调节，对转录、DNA 修复调节、端粒稳定性、细胞衰老和细胞凋亡有重要影响。在本研究中，使用 qPCR 评估了 37 例生长激素腺瘤和 31 例无功能垂体腺瘤（NFPAs）中的 SIRT1-7 mRNA 水平，并与肿瘤大小、侵袭性和 Ki-67 增殖指数进行了关联。生长激素腺瘤中 SIRT1 的过表达率为 86.5%，而 NFPAs 中为 41.9%（P<0.01）。与生长激素腺瘤相比，NFPAs 中 SIRT3 的表达明显下调（分别为 77.4%和 40.5%，P<0.01），SIRT4 和 SIRT7 也是如此。尽管 Sirtuins 与侵袭性或 Ki-67 指数之间没有关联，但 SIRT1 和 SIRT3 的表达与肿瘤大小有关。与 SIRT1 正常表达的腺瘤相比，SIRT1 过表达的腺瘤的最大直径平均值更小（P<0.01），SIRT3 低表达与较大的肿瘤有关（P<0.01）。总之，在垂体腺瘤中发现了 Sirtuins 表达的明显差异，表明这些基因是垂体腺瘤的潜在标志物，可用于生长激素腺瘤和 NFPAs 的特征分析。Sirtuins 在垂体肿瘤发病机制中的作用值得进一步研究，可能为其进展提供新的分子见解。
