Endocrine Abstracts

Context: Pathogenesis underlying non functioning pituitary adenoma (NFPA) formation and progression has not been well established. MEG3 is strongly expressed in the normal pituitary (NP) but not in NFPA derived from gonadotroph cells. High GSTP1 gene expression also seems to contribute to gonadotroph adenoma development. Recent reports indicate a role of miRNAs in the pituitary adenoma pathogenesis.

Objective: To evaluate the expression of MEG3, DLK1, GSTP1 genes and a panel of miRNAs and verify whether they correlate with clinical findings in NFPAs.

Material and Methods: MEG3, DLK1, GSTP1 genes and miRNAs were validated by real time PCR in 29NFPA and 15NP. GSTP1 protein was also evaluated by Western Blotting in 11NFPA with positive- (NFPA+), 11NFPA negative- (NFPA-) staining for glycoproteins, and 9NP.

Results: We observed underexpression of MEG3 (−13.5 fold; P=0.0004) and DLK1 (−100 fold; P<0.0001) genes and overexpression of GSTP1gene (4.8 fold; P=0.01) and its protein (P=0.04) in NFPAs. No expression of miR–21 and 145 and underexpression of miR-141, 16, let-7a, 133a, 150, 143 (ranging from −14.3 to −4.0–fold; P<0.002) were found in NFPAs. MEG3 underexpression and GSTP1 overexpression were associated with NFPA+ (P=0.004 and 0.05, respectively), which were also associated with bigger tumors (P=0.02). In addition, lower expression of miR–16 was associated with bigger tumors (P=0.01) and NFPA+ (P=0.03).

Conclusion: Our studies confirm that the loss of expression of DLK1 and MEG3 genes and overexpression of GSTP1 gene/protein are specifically important to the pathogenesis of NFPA+. Besides these genes, our data also show that miR143 underexpression seems to be involved in pathogenesis of NFPA+, while miR16 seems to regulate genes involved in controlling tumor size. In addition, we demonstrate that NFPA+ are bigger and have worse chance to achieve clinical control. These data shed lights on NFPA cytodifferentiation processes, which might improve future classification of its histotypes.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details unavailable.