CONTRIBUTION OF MITOCHONDRIAL FUNCTIONALITY IN GONADOTROPH PITUITARY NEUROENDOCRINE TUMORS

FERNANDEZ, S; BERTETTI, CB; RAMIREZ, J; BERNHARD, C; SOSA, LDV; VENIER, AC; PESAOLA, F; PALLA, V; LATINI, A; GRONDONA, E; DE PAUL, AL

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencias; 2023

Sociedad de Biociencia

Gonadotroph Pituitary Neuroendocrine Tumors (PitNETs) comprise one-third of all pituitary tumors and are categorized as non-function-ing PitNETs. Depending on the degree of invasion, they often cannot be completely removed through surgery. Metabolic reprogramming also plays a significant role in tumorigenesis. Mitochondria are pivotal in bioenergetics for tumor progression. Mitochondrial ultra-structure, composition, and functionality significantly vary in tumor contexts. In this context, we aimed to assess mitochondrial function-ality in gonadotropin PitNETs and analyze its implication in pituitary cell senescence. Samples from gonadotroph PitNETs (n=9) were immunolabeled for FSH, LH, and Ki-67; cell lineage was confirmed by ERα and GATA3. Tumor invasiveness was determined based on the Knosp classification. Protein fusion levels (Mfn1-2 and Opa-1) were assessed by western blot. Senescence-associated β-galacto-sidase (SA-β-Gal) expression was analyzed by colorimetric method in cryosections in cryosections. Mitochondrial number and morphol-ogy were evaluated through the analysis of 25 micrographs obtained by transmission electron microscope. Statistical and data analysis: Mann-Whitney test followed by Fisher’s test (post hoc); Image J and SPSS 23.0 software. In invasive gonadotroph, a higher num-ber of mitochondria with altered morphology (swelling), increased organelle area and perimeter, alongside elevated levels of Mfn1-2 and Opa-1 were observed. Conversely, expression of these fusion proteins and ultrastructural mitochondrial parameters were lower in non-invasive gonadotroph. SA-β-Gal expression was negative in the analyzed proliferative lesions. Our results suggest that mitochon-drial dynamics could be affected in invasive gonadotroph PitNETs. The increase in the expression of fusion proteins would reveal a strategy aimed at ensuring the energy supply to sustain pituitary tu-mor growth. The absence of SA-β-Gal expression, a hallmark of the senescent process, would indicate the evasion of this mechanism for controlling tumor growth.