Expressão de AMP-proteína quinase ativada (pAMPK) em adenomas hipofisários removidos cirurgicamente de pacientes com acromegalia

Abstract

Introduction: AMPK (AMP-activated protein kinase) is an enzyme that acts as a metabolic sensor by changing the ATP / AMP ratio and is related to the modulation of cell proliferation. The aim of this work was to study the expression of pAMPK in sporadic growth hormone-secreting pituitary adenomas (GH). We also evaluated the expression of pAMPK in tumor somatotrophic cells of patients with acromegaly with mutation of the AIP and GNAS gene, in addition to the correlation between the expression of pAMPK and the following clinical parameters: sex; body mass index (BMI); cytokeratin expression pattern (CAM5.2); use of metformin before surgery; preoperative GH levels and the need to use drug therapy (somatostatin analogue or cabergoline) after surgery. Methods: We included to the study, biopsies of patients diagnosed with acromegaly and who underwent surgery to remove the adenoma (n = 16), normal pituitary glands without structural or endocrine alteration (n = 5) and growth hormone -secreting adenomas with AIP mutation (Q164X, R304 *, R304Q, E222 * and F269_H275dup). The biopsies of patients diagnosed with acromegaly were also submitted to the study to determine the presence of the GNAS mutation. Results: Expression of pAMPK was significantly higher in patients with acromegaly compared to normal pituitary glands (p <0.0001). The clinical parameters of patients with acromegaly: gender, BMI, expression pattern of cytokeratin CAM5.2, use of metformin before surgery, GH levels before surgery and need for drug therapy (somatostatin analogue or cabergoline) after surgery did not show statistical correlation with the expression of pAMPK in the somatotrophic cells of the adenomas of patients with acromegaly in the evaluated sample. The GNAS mutation was observed in only one patient, who showed pAMPK expression similar to patients with acromegaly without this mutation. The AIP R304 *, Q164X, and F269_H275dup mutations showed pAMPK expression equal to adenomas without mutation of this gene. Mutations E222 * and R304Q, on the other hand, showed significantly increased pAMPK expression in comparison to adenomas without mutation in this gene (p <0.0001). Conclusion: Our data show an increase in the expression of pAMPK in sporadic somatotropinomas, regardless of the preoperative use of metformin.