ECE2013 Poster Presentations Adrenal cortex (64 abstracts)
The gene expression profile of cortisol secretion in adrenocortical adenomas
Hortense Wilmot Roussel 1, , Delphine Vezzosi 1, , Marthe Rizk-Rabin 1 , Olivia Barreau 1, , Bruno Ragazzon 1 , Fernande René-Corail 1 , Aurélien de Reynies 4 , Jérôme Bertherat 1, & Guillaume Assié 1,
1Inserm U1016, CNRS UMR 8104, Faculté de Médecine Paris Descartes, Institut Cochin, Université Paris Descartes, Paris, France; 2Department of Endocrinology, Hôpital Larrey, Toulouse, France; 3Department of Endocrinology, Reference Center for Rare Adrenal Diseases, Assistance Publique Hôpitaux de Paris, Hôpital Cochin, Paris, France; 4Plateforme de Bioinformatique, Carte d’Identité des Tumeurs, Ligue contre le Cancer, Paris, France.
The cortisol secretion level of adrenocortical adenomas range from hormonally silent to overt hypercortisolism. The mechanisms leading to the autonomous hypersecretion of cortisol are unknown. The aim was to identify the gene expression alterations associated with the autonomous and excessive cortisol secretion of adrenocortical adenomas.
Methods: The transcriptome of 22 unilateral adrenocortical adenomas (5 non-secreting, 6 subclinical cortisol-producing, and 11 cortisol-producing) was studied and correlated with cortisol secretion. Phosphodiesterase 8B (PDE8B) expression was measured by Western Blot.
Results: 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.
Conclusion: 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 seem altered in cortisol secreting adenomas.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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