Morphological and molecular evidence of macroautophagy in pituitary tumors

L. Cecenarro*^a (Dr), G. Moyano Crespo^b (Dr), C. Guido^b (Dr), P. Pérez^b (Dr), F. Picech^b (Dr), JC. De Battista^a (Dr), JP. Petiti^b (Dr), JH. Mukdsi^b (Dr)

^a Hospital Privado Universitario de Córdoba, Córdoba, ARGENTINA ; ^b Centro de Microscopía Electrónica, Instituto de Investigaciones en Ciencias de la Salud (INICSA- CONICET), Facultad de Ciencias Médicas, Universidad Nacional de Córdoba., Córdoba, ARGENTINA

* lurycece@gmail.com

Introduction: Macroautophagy constitutes a lysosome-mediated degradation process that controls the quality of cytoplasmic components and organelles being a well-regulated process is under the control of autophagy related proteins, Beclin1/Atg6 and LC3/Atg8. PitNETs are very common and benign, although some of them can be locally aggressive and metastasize. Reports on macroautophagy in the field of pituitary neuroendocrinology are scarce. With this aim, our study analysed the morphological and molecular evidence of macroautophagy, determining the expression of Beclin1 and LC3 proteins in experimental tumours and human functioning PitNETs. Methods: Our investigation focused on the occurrence of macroautophagy using TEM, IF and WB throughout pituitary tumor development (estrogen induced prolactinoma) and in a series of human functioning PitNETs (n:33), at correlated Beclin1 and LC3 expression with the clinico-pathological data of the patients. Results: In the experimental prolactinoma and in the functioning human PitNETs, vesicular elements compatible with autophagosomes were observed at the subcellular level, with the highest Beclin1 level at 20 days of hormonal stimulation (hyperplastic adenomatous stage), and LC3 at 30 days (adenomatous glandular stage). In the murine model, protein expression was associated with increased glandular size and weight, and in human PitNETs, statistical analysis revealed a significant difference for Beclin 1 and LC3 between macro and microadenomas (p < 0.05). Conclusion: Macroautophagy is a cellular and molecular mechanism that participates in the pituitary tumour development, being linked to the macroadenomas, and acting on the control of tumour growth, turning this mechanism could be beneficial in regulating pituitary cell growth. Bibliography: 1. Asa SL, Casar-Borota O, Chanson P, Delgrange E, Earls P, Ezzat S, et. al.; attendees of 14th Meeting of the International Pituitary Pathology Club, Annecy, France, November 2016. From pituitary adenoma to pituitary neuroendocrine tumor (PitNET): an International Pituitary Pathology Club proposal. Endocr Relat Cancer. 2017 Apr;24(4):C5-C8. 2.Weckman A, Di Ieva A, Rotondo F, Syro LV, Ortiz LD, Kovacs K, et al. Autophagy in the endocrine glands. J Mol Endocrinol. 2014 Feb 24;52(2): R151-63.

The author has declared no conflict of interest.