持续的生长激素 (GH) 在非GH缺乏小鼠的生长期间对肝脏的影响
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Verónica G Piazza1, Nadia S Cicconi1, Mariana A Bojorge1
1Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, Consejo Nacional de Investigaciones Científicas y Técnicas, Instituto de Química y Fisicoquímica Biológicas (IQUIFIB, UBA-CONICET), Universidad de Buenos Aires, Buenos Aires, Argentina.
在非GH缺乏的小鼠中,持续给予生长激素 (GH) 并没有促进生长,但改变了肝脏基因表达,可能增加癌症风险. 需要进一步的研究来了解这些亲瘤的信号通路.
科学领域:
- 内分泌学 在内分泌学.
- 分子生物学分子生物学
- 在瘤学瘤学.
背景情况:
- 增长激素 (GH) 用于促进儿童的生长,但标准的每日注射是繁的.
- 长效的GH配方是可取的,但在非GH缺乏的人群中,更高的剂量可能会带来癌症风险.
- GH的作用是两性异形的,因此需要在男性和女性受试者身上进行研究.
研究的目的:
- 评估持续GH在非GH缺乏小鼠的肝脏中持续GH的潜在亲瘤效应.
- 研究连续GH对肝脏基因表达和信号通路的影响.
- 评估肝脏对连续GH的反应的性别特异性差异.
主要方法:
- 在成长期间,小鼠使用透式迷你连续5周注入GH (6μg/gBW).
- 从出生开始就监测身体的生长,并在8周大时分析肝脏组织.
- 评估了肝脏基因表达,蛋白质酸化 (STAT3,STAT5) 和细胞增殖标志物 (PCNA).
主要成果:
- 持续的GH输液未能促进非GH缺少小鼠的身体生长.
- 在男性中,GH治疗增加了肝细胞增殖率 (PCNA).
- 连续的GH激活了女性的STAT3,并诱导了肝脏基因表达的性别特异性变化,包括IGF1,cyclin D1,MUP,EGFR,GHR,SOCS2,c-myc和CIS.
结论:
- 连续的GH给药,即使是间歇有效的剂量,在非GH缺乏的条件下也不会增强生长.
- 这种治疗方案可能会诱导肝脏的分子变化,暗示有亲瘤信号.
- 这些发现突出了与持续GH使用相关的潜在风险,并强调了GH治疗中剂量和剂量模式的重要性.
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