The Mechanisms Underlying Autonomous Adrenocorticotropic Hormone Secretion in Cushing's Disease.
ACTH Syndrome, Ectopic
/ diagnosis
ACTH-Secreting Pituitary Adenoma
/ diagnosis
Adrenocorticotropic Hormone
/ biosynthesis
Biomarkers
Cushing Syndrome
/ diagnosis
Diagnosis, Differential
Disease Susceptibility
Female
Gene Expression Regulation
Glucocorticoids
/ metabolism
Humans
Male
Signal Transduction
Cushing’s disease
adrenocorticotrophic hormone
ectopic ACTH syndrome
glucocorticoid resistance
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
30 Nov 2020
30 Nov 2020
Historique:
received:
20
10
2020
revised:
21
11
2020
accepted:
29
11
2020
entrez:
3
12
2020
pubmed:
4
12
2020
medline:
9
3
2021
Statut:
epublish
Résumé
Cushing's disease caused due to adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas (ACTHomas) leads to hypercortisolemia, resulting in increased morbidity and mortality. Autonomous ACTH secretion is attributed to the impaired glucocorticoid negative feedback (glucocorticoid resistance) response. Interestingly, other conditions, such as ectopic ACTH syndrome (EAS) and non-neoplastic hypercortisolemia (NNH, also known as pseudo-Cushing's syndrome) also exhibit glucocorticoid resistance. Therefore, to differentiate between these conditions, several dynamic tests, including those with desmopressin (DDAVP), corticotrophin-releasing hormone (CRH), and Dex/CRH have been developed. In normal pituitary corticotrophs, ACTH synthesis and secretion are regulated mainly by CRH and glucocorticoids, which are the ACTH secretion-stimulating and -suppressing factors, respectively. These factors regulate ACTH synthesis and secretion through genomic and non-genomic mechanisms. Conversely, glucocorticoid negative feedback is impaired in ACTHomas, which could be due to the overexpression of 11β-HSD2, HSP90, or TR4, or loss of expression of CABLES1 or nuclear BRG1 proteins. Genetic analysis has indicated the involvement of several genes in the etiology of ACTHomas, including
Identifiants
pubmed: 33266265
pii: ijms21239132
doi: 10.3390/ijms21239132
pmc: PMC7730156
pii:
doi:
Substances chimiques
Biomarkers
0
Glucocorticoids
0
Adrenocorticotropic Hormone
9002-60-2
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Grant-in-Aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology
ID : 19K09003
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