Steroidogenomics analysis of adrenal steroid excess – STEROMICS
Steroidogenomics analysis of adrenal steroid excess
Adrenal steroids control many physiological process and are altered in many diseases. Adrenal diseases causing steroid excess are<br />good models to study steroids synthesis and its dysregulation.
To understand the mechanisms of adrenal stéroid excess
The morbidity and mortality associated with excess adrenal steroids is significant in the absence of treatment.Getting a better understanding of the mechanisms of these disturbances would allow to manage them more effectively and generally to better understand frequent pathologies in which disturbances. of these steroids are also seen.
We will combine high-throughput approaches from genomics and steroid mass spectrometry studies to establish profiles of molecular abnormalities associated with steroid profiles in different adrenal pathologies. The studies will be carried out in parallel with the different «omics« on the same tissue fragments of adenoma and adrenal hyperplasia, representing a
wide spectrum of steroidogenesis abnormalities. The results of these high-throughput analyzes will be integrated by bioinformatics analysis
to identify the genetic and epigenetic determinants of steroidogenesis abnormalities.
At the 18-month stage of the project, we characterized molecular classes of benign adrenal tumors correlating with disruption of steroid secretion.
This will allow progress in the pathophysiology of steroid disorders observed in adrenal diseases and open perspectives in many non-adrenal metabolic or cardiovascular diseases where adrenal steroid abnormalities have been observed.
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3. Chortis V, Bancos I, Nijman T,...,Bertherat J, Beuschlein F, Fassnacht M, Deeks JJ, Biehl M, Arlt W. Urine Steroid Metabolomics as a Novel Tool for Detection of Recurrent Adrenocortical Carcinoma. J Clin Endocrinol Metab. 2020 Mar 1;105(3):e307–18.
4. Le Mestre J, Duparc C, Reznik Y, Bonnet-Serrano F, ...,..., Bertherat J, Lefebvre H, Louiset E. Illicit Upregulation of Serotonin Signaling Pathway in Adrenals of Patients With High Plasma or Intra-Adrenal ACTH Levels. J Clin Endocrinol Metab. 2019 Nov 1;104(11):4967-4980.
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6. Faillot S, Foulonneau T, Néou M, Espiard S, Garinet S, Vaczlavik A, Jouinot A, Rondof W, Septier A, Drougat L, Hécale-Perlemoine K, Ragazzon B, Rizk-Rabin M, Sibony M, Bonnet-Serrano F, Guibourdenche J, Libé R, Groussin L, Dousset B, de Reyniès A, Bertherat J, Assié G. Genomic classification of benign adrenocortical lesions. Endocr Relat Cancer. 2021 Jan;28(1):79-95.
7. Vaduva P, Bonnet F, Bertherat J. Molecular Basis of Primary Aldosteronism and Adrenal Cushing Syndrome. J Endocr Soc. 2020 Jun 29;4(9):bvaa075.
8. Hannah-Shmouni F, Berthon A, Faucz FR, Briceno JM, ..., Bonnet-Serrano F, Vaczlavik A, Bertherat J, Reincke M, Eisenhofer G, Stratakis CA. Mass spectrometry-based steroid profiling in primary bilateral macronodular adrenocortical hyperplasia. Endocr Relat Cancer. 2020 Jul;27(7):403-413.
Adrenal steroids control many physiological process and are altered in many diseases. Adrenal diseases causing steroid excess are
good models to study steroids synthesis and its dysregulation. Our aim is to understand the molecular mechanisms of adrenal
steroid dysregulation by combining various high-throughput genomics and steroidomics (mass spectrometry analysis) approaches.
We will use macronodular- and micronodular- adrenal hyperplasia as well as adrenal adenomas as models of a broad range of
steroids dysregulation. We will study the genomics (transcriptome, miRnome, methylome, snp, ngs), steroidomics (targeted and
non-targeted), and perform functional studies of steroids secretion in parallel on the same series of adrenal tissues. The integration
of theses various “omics” will allow to identify specific molecular and steroid profiles of steroid dysregulation. This will open new
perspectives to progress in the pathophysiology of various diseases associated with steroid exces
Project coordination
Jérôme BERTHERAT (INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE)
The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.
Partnership
INSERM INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
DC2N Différenciation et Communication Neuronale et Neuroendocrine
University of Birmingham / Institute of Metabolism and Systems Research
Help of the ANR 406,404 euros
Beginning and duration of the scientific project:
January 2019
- 48 Months