Androgen production in pediatric adrenocortical tumors may occur via both the classic and/or the alternative backdoor pathway.

Marti, Nesa Magdalena; Malikova, Jana; Galván Hernández, José Alberto; Aebischer, Maude; Janner, Marco; Sumnik, Zdenek; Obermannova, Barbora; Escher, Geneviève; Perren, Aurel; Flück Pandey, Christa Emma (2017). Androgen production in pediatric adrenocortical tumors may occur via both the classic and/or the alternative backdoor pathway. Molecular and cellular endocrinology, 452, pp. 64-73. Elsevier Ireland 10.1016/j.mce.2017.05.014

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Children with adrenocortical tumors (ACTs) often present with virilization due to high tumoral androgen production, with dihydrotestosterone (DHT) as most potent androgen. Recent work revealed two pathways for DHT biosynthesis, the classic and the backdoor pathway. Usage of alternate routes for DHT production has been reported in castration-resistant prostate cancer, CAH and PCOS. To assess whether the backdoor pathway may contribute to the virilization of pediatric ACTs, we investigated seven children suffering from androgen producing tumors using steroid profiling and immunohistochemical expression studies. All cases produced large amounts of androgens of the classic and/or backdoor pathway. Variable expression of steroid enzymes was observed in carcinomas and adenomas. We found no discriminative pattern. This suggests that enhanced androgen production in pediatric ACTs is the result of deregulated steroidogenesis through multiple steroid pathways. Thus future treatments of ACTs targeting androgen overproduction should consider these novel steroid production pathways.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Nephrology and Hypertension
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Nephrologie / Hypertonie
04 Faculty of Medicine > Other Institutions > Teaching Staff, Faculty of Medicine
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Endokrinologie / Diabetologie / Metabolik (Pädiatrie)
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Pavillon 52 > Endokrinologie / Diabetologie (Erwachsene)
04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Marti, Nesa Magdalena; Malikova, Jana; Galván Hernández, José Alberto; Aebischer, Maude; Janner, Marco; Escher, Geneviève; Perren, Aurel and Flück Pandey, Christa Emma

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology

ISSN:

0303-7207

Publisher:

Elsevier Ireland

Language:

English

Submitter:

Aurel Perren

Date Deposited:

09 Oct 2017 17:28

Last Modified:

29 Jan 2018 11:12

Publisher DOI:

10.1016/j.mce.2017.05.014

PubMed ID:

28501574

Uncontrolled Keywords:

Alternative (backdoor) pathway Androgen biosynthesis Classic pathway Dihydrotestosterone Pediatric adrenocortical tumors

BORIS DOI:

10.7892/boris.106015

URI:

https://boris.unibe.ch/id/eprint/106015

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