Περίληψη:
Although the effect of the central clock system on adrenal function has been extensively studied, the role of the peripheral clock system in adrenal tumorigenesis remains largely unexplored. In this study we investigated the expression of clock-related genes in normal adrenocortical tissue and adrenocortical tumors. Twenty-seven fresh frozen human adrenal tissues including 13 cortisol secreting adenomas (CSA), seven aldosterone producing adenomas (APA), and seven adrenocortical carcinomas (ACC) were collected. CLOCK, BMAL1, PER1, CRY1, Rev-ERB, and RORα mRNA and protein expression were determined by qPCR and immunoblotting in pathological tissues and compared with the adjacent normal adrenal tissues. A significant downregulation of PER1, CRY1, and Rev-ERB compared with their normal tissue was demonstrated in CSA. All clock-related genes were overexpressed in APA compared with their normal tissue, albeit not significantly. A significant upregulation of CRY1 and PER1 and downregulation of BMAL1, RORα, and Rev-ERB compared with normal adrenal tissue was observed in ACC. BMAL1 and PER1 were significantly downregulated in APA compared with CSA. CLOCK, CRY1, and PER1 were upregulated, whereas BMAL1, RORα, and Rev-ERB were downregulated in ACC compared with CSA. Our study demonstrated the expression of CLOCK, BMAL1, PER1, CRY1, Rev-ERB, and RORα in normal and pathological human adrenal tissues. Adrenal tumors exhibited altered expression of these genes compared with normal tissue, with specific differences between benign and malignant lesions and between benign tumors arising from glomerulosa vs fasciculata zone. Further studies should clarify whether these alterations could be implicated in adrenocortical tumorigenesis. © 2020, Springer Science+Business Media, LLC, part of Springer Nature.
Συγγραφείς:
Angelousi, A.
Nasiri-Ansari, N.
Karapanagioti, A.
Kyriakopoulos, G.
Aggeli, C.
Zografos, G.
Choreftaki, T.
Parianos, C.
Kounadi, T.
Alexandraki, K.
Randeva, H.S.
Kaltsas, G.
Papavassiliou, A.G.
Kassi, E.
Λέξεις-κλειδιά:
cryptochrome 1; estrogen receptor beta; messenger RNA; PER1 protein; retinoid related orphan receptor alpha; transcription factor ARNTL; transcription factor CLOCK, adrenal cortex; adrenal cortex carcinoma; adrenal cortex tumor; adrenal gland tissue; adult; Article; BMAL1 gene; circadian rhythm; clinical article; CLOCK gene; controlled study; cortisol secreting adenoma; cross-sectional study; CRY1 gene; disease association; down regulation; female; gene; gene expression; gene expression regulation; gene overexpression; genetic analysis; genetic association; human; human cell; human tissue; immunoblotting; male; middle aged; PER1 gene; primary hyperaldosteronism; priority journal; protein expression; real time polymerase chain reaction; Rev ERB gene; RORalpha gene; tumor differentiation; upregulation; zona fasciculata; zona glomerulosa