PMID- 36716712 OWN - NLM STAT- MEDLINE DCOM- 20230705 LR - 20230705 IS - 1423-0194 (Electronic) IS - 0028-3835 (Linking) VI - 113 IP - 7 DP - 2023 TI - Ultrastructural and Molecular Evidence of Macroautophagy in Functioning PitNETs and Experimental Pituitary Tumors. PG - 705-718 LID - 10.1159/000529416 [doi] AB - INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. CI - (c) 2023 S. Karger AG, Basel. FAU - Cecenarro, Laura Anahi AU - Cecenarro LA AD - Centro de Microscopia Electronica, Facultad de Ciencias Medicas, Universidad Nacional de Cordoba, Cordoba, Argentina. AD - Hospital Privado Universitario de Cordoba, Cordoba, Argentina. FAU - Moyano Crespo, Gabriela Deisi AU - Moyano Crespo GD AD - Centro de Microscopia Electronica, Facultad de Ciencias Medicas, Universidad Nacional de Cordoba, Cordoba, Argentina. FAU - Guido, Carolina Beatriz AU - Guido CB AD - Centro de Microscopia Electronica, Facultad de Ciencias Medicas, Universidad Nacional de Cordoba, Cordoba, Argentina. FAU - Perez, Pablo Anibal AU - Perez PA AD - Centro de Microscopia Electronica, Facultad de Ciencias Medicas, Universidad Nacional de Cordoba, Cordoba, Argentina. AD - Instituto de Investigaciones en Ciencias de la Salud (INICSA), Consejo Nacional de Investigaciones Cientificas y Tecnicas, Cordoba, Argentina. FAU - Faure, Erica Elizabeth AU - Faure EE AD - Centro de Microscopia Electronica, Facultad de Ciencias Medicas, Universidad Nacional de Cordoba, Cordoba, Argentina. FAU - Picech, Florencia AU - Picech F AD - Centro de Microscopia Electronica, Facultad de Ciencias Medicas, Universidad Nacional de Cordoba, Cordoba, Argentina. FAU - Rossetto, Sofia Victoria AU - Rossetto SV AD - Centro de Microscopia Electronica, Facultad de Ciencias Medicas, Universidad Nacional de Cordoba, Cordoba, Argentina. AD - Instituto de Investigaciones en Ciencias de la Salud (INICSA), Consejo Nacional de Investigaciones Cientificas y Tecnicas, Cordoba, Argentina. FAU - De Battista, Juan Carlos AU - De Battista JC AD - Hospital Privado Universitario de Cordoba, Cordoba, Argentina. FAU - Gutierrez, Silvina AU - Gutierrez S AD - Centro de Microscopia Electronica, Facultad de Ciencias Medicas, Universidad Nacional de Cordoba, Cordoba, Argentina. AD - Instituto de Investigaciones en Ciencias de la Salud (INICSA), Consejo Nacional de Investigaciones Cientificas y Tecnicas, Cordoba, Argentina. FAU - Torres, Alicia Ines AU - Torres AI AD - Centro de Microscopia Electronica, Facultad de Ciencias Medicas, Universidad Nacional de Cordoba, Cordoba, Argentina. AD - Instituto de Investigaciones en Ciencias de la Salud (INICSA), Consejo Nacional de Investigaciones Cientificas y Tecnicas, Cordoba, Argentina. FAU - Petiti, Juan Pablo AU - Petiti JP AD - Centro de Microscopia Electronica, Facultad de Ciencias Medicas, Universidad Nacional de Cordoba, Cordoba, Argentina. AD - Instituto de Investigaciones en Ciencias de la Salud (INICSA), Consejo Nacional de Investigaciones Cientificas y Tecnicas, Cordoba, Argentina. FAU - Mukdsi, Jorge Humberto AU - Mukdsi JH AD - Centro de Microscopia Electronica, Facultad de Ciencias Medicas, Universidad Nacional de Cordoba, Cordoba, Argentina. AD - Instituto de Investigaciones en Ciencias de la Salud (INICSA), Consejo Nacional de Investigaciones Cientificas y Tecnicas, Cordoba, Argentina. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230130 PL - Switzerland TA - Neuroendocrinology JT - Neuroendocrinology JID - 0035665 RN - 0 (Beclin-1) RN - 0 (Microtubule-Associated Proteins) SB - IM MH - Humans MH - Rats MH - Animals MH - Beclin-1 MH - *Macroautophagy MH - *Pituitary Neoplasms MH - Rats, Inbred F344 MH - Autophagy MH - Microtubule-Associated Proteins/metabolism MH - Mammals/metabolism OTO - NOTNLM OT - Beclin1 OT - Electronmicroscopy OT - LC3II OT - Macroautophagy OT - Pituitary tumor EDAT- 2023/01/31 06:00 MHDA- 2023/07/05 06:42 CRDT- 2023/01/30 18:22 PHST- 2022/04/26 00:00 [received] PHST- 2023/01/23 00:00 [accepted] PHST- 2023/07/05 06:42 [medline] PHST- 2023/01/31 06:00 [pubmed] PHST- 2023/01/30 18:22 [entrez] AID - 000529416 [pii] AID - 10.1159/000529416 [doi] PST - ppublish SO - Neuroendocrinology. 2023;113(7):705-718. doi: 10.1159/000529416. Epub 2023 Jan 30.