Introduction: Previous results of our group, presented in the ECE last year, showed a lower gene expression of proconvertase PC1/3, involved in the processing of POMC, in silent corticotroph tumors (sCT) than in functioning ones (fCT), overall and in microadenomas. The aim of the present study was to quantify the protein expression of convertases involved in the processing of POMC (PC1/3) and in the degradation of ACTH (PC2, CPE and PAM) in a series of CT.
Methods: We selected 15 sCT, 15 fCT and 14 silent gonadotroph tumors (sGT) (control group). Previously, the gene expression of these convertases was quantified by quantitative PCR. The quantification of protein expression was carried out by Western Blot.
Results: Similar to gene expression studies, sCT showed lower PC1/3 protein expression than fCT (P=0.078), especially than fCT microadenomas (P=0.028). Moreover, we observed a strong positive correlation between PC2 and CPE gene and protein expression (ρ≥0.670, P<0.009) in sCT but a lack of correlation in the case of PC1/3.
Conclusion: The difference in PC1/3 expression between sCT and fCT remains at the proteins level. This low gene and protein PC1/3 expressions and the efficient post-transcriptional processing of PC2 and CPE in sCT compared with fCT could explain the lack of Cushing symptomatology in sCT. Moreover, we confirmed that the macro CT represent an intermediate state between silent and micro fCT.
Grant from the CIBERER (Rare Disease Network of Excellence) ER15TRL2EOI9/2017.
18 - 21 May 2019
European Society of Endocrinology