Cholesterol deprivation drives DHEA biosynthesis in human adrenals.

Pignatti, Emanuele; Altinkiliç, Emre Murat; Bräutigam, Konstantin; Grössl, Michael; Perren, Aurel; Zavolan, Mihaela; Flück, Christa E (2022). Cholesterol deprivation drives DHEA biosynthesis in human adrenals. Endocrinology, 163(7) Endocrine Society 10.1210/endocr/bqac076

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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.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine 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) 04 Faculty of Medicine > Service Sector > Institute of Pathology 04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine > Endocrinology/Metabolic Disorders 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Endokrinologie / Diabetologie / Metabolik (Pädiatrie) 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Nephrologie / Hypertonie
UniBE Contributor:	Pignatti, Emanuele (B), Altinkiliç, Emre Murat, Bräutigam, Konstantin, Grössl, Michael, Perren, Aurel, Flück Pandey, Christa Emma
Subjects:	600 Technology > 610 Medicine & health 500 Science > 570 Life sciences; biology
ISSN:	0013-7227
Publisher:	Endocrine Society
Language:	English
Submitter:	Anette van Dorland
Date Deposited:	19 May 2022 10:26
Last Modified:	05 Dec 2022 16:19
Publisher DOI:	10.1210/endocr/bqac076
PubMed ID:	35583599
Uncontrolled Keywords:	DHEA adrenarche cholesterol
URI:	https://boris.unibe.ch/id/eprint/170112