Abstract | CONTEXT: OBJECTIVE: The objective of the study was to identify the gene expression profile associated with the autonomous and excessive cortisol secretion of adrenocortical adenomas. PATIENTS AND METHODS: RESULTS: Unsupervised clustering identified 2 groups of adenomas with a difference in secretion level (P = .008). Cluster 1 included only cortisol-producing adenomas (8 of 11), whereas cluster 2 was an admixture of the nonsecreting, the subclinical cortisol-secreting, and 3 of the 11 cortisol-secreting adenomas (Fisher exact, P = .002). This cluster was driven by genes related to cortisol secretion and to extracellular matrix. More than 3000 genes correlated with cortisol secretion. Among the positively correlated were the steroidogenic enzymes, genes involved in cholesterol metabolism, and glutathione S- transferases. Among the negatively correlated genes were genes related to transcripts translation and the transcription factor GATA-6. The PDE8B, which inactivates the protein kinase A pathway, unexpectedly showed the strongest positive correlation with cortisol secretion, confirmed by Western blot. The protein kinase A-activity to cAMP ratio was increased in adenomas with high PDE8B levels, suggesting counterregulation to limit downstream activation of the pathway. CONCLUSION:
|
Authors | Hortense Wilmot Roussel, Delphine Vezzosi, Marthe Rizk-Rabin, Olivia Barreau, Bruno Ragazzon, Fernande René-Corail, Aurélien de Reynies, Jérôme Bertherat, Guillaume Assié |
Journal | The Journal of clinical endocrinology and metabolism
(J Clin Endocrinol Metab)
Vol. 98
Issue 6
Pg. E1109-21
(Jun 2013)
ISSN: 1945-7197 [Electronic] United States |
PMID | 23539725
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Glutathione Transferase
- 3',5'-Cyclic-AMP Phosphodiesterases
- PDE8B protein, human
- Hydrocortisone
|
Topics |
- 3',5'-Cyclic-AMP Phosphodiesterases
(genetics)
- Adrenal Cortex Neoplasms
(genetics, metabolism)
- Adrenocortical Adenoma
(genetics, metabolism)
- Adult
- Aged
- Female
- Glutathione Transferase
(physiology)
- Humans
- Hydrocortisone
(metabolism)
- Male
- Middle Aged
- Transcriptome
|