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Cholesterol deprivation drives DHEA biosynthesis in human adrenals

Pignatti, Emanuele and Altinkilic, Emre Murat and Bräutigam, Konstantin and Grössl, Michael and Perren, Aurel and Zavolan, Mihaela and Flück, Christa E.. (2022) Cholesterol deprivation drives DHEA biosynthesis in human adrenals. Endocrinology, 163 (7). bqac076.

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Official URL: https://edoc.unibas.ch/88442/

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Abstract

Adrenarche is an early event in sexual maturation in prepubertal children and corresponds to the postnatal development of the adrenocortical zona Reticularis (zR). Still, the molecular mechanisms that govern the onset and maturation of zR remain unknown. Using tissue laser microdissection combined with transcript quantification and immunodetection, we showed that the human zR receives low levels of cholesterol in comparison to other adrenal layers. To model this metabolic condition, we challenged adrenal cells in vitro using cholesterol deprivation. This resulted in reprogramming the steroidogenic pathway towards inactivation of 3-beta-hydroxysteroid dehydrogenase type 2 (HSD3B2), increased CYB5A expression, and increased biosynthesis of Dehydroepiandrosterone (DHEA), three key features of zR maturation during adrenarche. Finally, we found that cholesterol deprivation leads to decreased transcriptional activity of POU3F2, which normally stimulates the expression of HSD3B2 by directly binding to its promoter. These findings demonstrate that cholesterol deprivation can account, at least in part, for the acquisition of a zR-like androgenic program in humans.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Computational & Systems Biology > Bioinformatics (Zavolan)
UniBasel Contributors:Zavolan, Mihaela
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Oxford University Press
ISSN:0013-7227
e-ISSN:1945-7170
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:26 Jul 2022 07:24
Deposited On:26 Jul 2022 07:24

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