Session: SUN 17-28-Adrenal Tumors & Pheochromocytoma
Poster Board SUN-23
The transcriptome of 22 unilateral adrenocortical adenomas (5 non-secreting, 6 subclinical cortisol-producing, 11 cortisol-producing) was studied and correlated with cortisol secretion. Phosphodiesterase 8B (PDE8B) expression was measured by Western Blot.
Unsupervised hierarchical clustering identifies two groups of adenomas with a difference in secretion level (p=0.008). Cluster 1 includes only cortisol-producing adenomas (8 out of 11), while Cluster 2 is an admixture of the non-secreting, the subclinical cortisol-secreting and 3 of the 11 cortisol-secreting adenomas (Fisher exact p=0.002). This cluster is driven by genes related to cortisol secretion and to extracellular matrix.
More than three thousand genes correlate with cortisol secretion. Among the positively correlated are the steroidogenic enzymes, genes involved in cholesterol metabolism and glutathione S-transferases. Among the negatively correlated genes are genes related to transcripts translation and the transcription factor GATA-6.
The PDE8B, which inactivates the PKA pathway, unexpectedly showed the strongest positive correlation with cortisol secretion, confirmed by Western Blot. The PKA-activity/cAMP ratio was increased in adenomas with high PDE8B levels, suggesting that the PDE8B increase is a counter-regulation to limit downstream activation of the pathway.
The transcriptome of adrenocortical adenomas shows a major association with cortisol secretion and identifies specific groups of genes implicated in steroid secretion. Among them, the cAMP/PKA pathway seems altered in cortisol secreting adenomas.
Nothing to Disclose: GA, HW, DV, MR, OB, BR, FR, AD, JYB
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