Centro de Microscopía Electrónica, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
Hospital Privado Universitario de Córdoba, Córdoba, Argentina.
Neuroendocrinology. 2023;113(7):705-718. doi: 10.1159/000529416. Epub 2023 Jan 30.
Macroautophagy is a lysosome-mediated degradation process that controls the quality of cytoplasmic components and organelles, with its regulation depending on autophagy-related proteins (Atg) and with Beclin1/Atg6 and microtubule-associated protein light chain 3 (LC3/Atg8) being key players in the mammalian autophagy. As reports on this mechanism in the field of pituitary neuropathology and neuroendocrinology are scarce, our study analyzed the ultrastructural signs of macroautophagy and the expression of Beclin1 and LC3 proteins in human functioning PitNETs and in experimental pituitary tumors.
A group of humans functioning PitNETs and an experimental lactotroph model in rats of the F344 strain stimulated with estradiol benzoate (BE) were used. Ultrastructural and molecular evidence of the macroautophagic process was evaluated using different techniques.
In functioning PitNETs cohort, 60% exhibited evidence of macroautophagy, with a significant difference found for Beclin1 and LC3 between macro- and micro-PitNETs (p < 0.05). In the experimental model, the expression of both Beclin1 and LC3 proteins was immunopositive in normal and tumoral glands when analyzed by immunofluorescence, Western blot, and immunohistochemistry. In the experimental model, protein expression was associated with increased glandular size and weight.
Our study revealed evidence of macroautophagy at the pituitary level and the important role of Beclin1 and LC3 in the progression of functioning PitNETs, implying that this mechanism participate in regulating pituitary cell growth.
巨自噬是一种溶酶体介导的降解过程，可控制细胞质成分和细胞器的质量，其调节取决于自噬相关蛋白 (Atg)，并且 Beclin1/Atg6 和微管相关蛋白轻链 3 (LC3/Atg8) 是哺乳动物自噬的关键参与者。由于该机制在垂体神经病理学和神经内分泌学领域的报道很少，因此我们的研究分析了巨自噬的超微结构特征以及人类功能性 PitNETs 和实验性垂体肿瘤中 Beclin1 和 LC3 蛋白的表达。
使用一组人类功能性 PitNETs 和用苯甲酸雌二醇 (BE) 刺激的 F344 大鼠的实验性催乳素瘤模型。使用不同的技术评估巨自噬过程的超微结构和分子证据。
在功能性 PitNETs 队列中，有 60%表现出巨自噬的证据，Macro- 和 Micro-PitNETs 之间的 Beclin1 和 LC3 差异有统计学意义 (p < 0.05)。在实验模型中，通过免疫荧光、Western blot 和免疫组织化学分析，正常和肿瘤腺体中 Beclin1 和 LC3 两种蛋白的表达均呈免疫阳性。在实验模型中，蛋白表达与腺体大小和重量的增加有关。
我们的研究揭示了垂体水平巨自噬的证据，以及 Beclin1 和 LC3 在功能性 PitNETs 进展中的重要作用，这意味着该机制参与调节垂体细胞的生长。
