2. Academic Validation
  3. Cholesterol Deprivation Drives DHEA Biosynthesis in Human Adrenals

Cholesterol Deprivation Drives DHEA Biosynthesis in Human Adrenals

  • Endocrinology. 2022 Jul 1;163(7):bqac076. doi: 10.1210/endocr/bqac076.
Emanuele Pignatti 1 2,  Emre Murat Altinkilic 1 3,  Konstantin Bräutigam 4,  Michael Grössl 3 5,  Aurel Perren 6,  Mihaela Zavolan 7,  Christa E Flück 1 2
Affiliations

Affiliations

  • 1 Division of Pediatric Endocrinology, Diabetology and Metabolism, Department of Pediatrics, University Hospital Inselspital, University of Bern, 3010 Bern, Switzerland.
  • 2 Department for BioMedical Research, University Hospital Inselspital, University of Bern, 3010 Bern, Switzerland.
  • 3 Department for BioMedical Research, University Hospital Inselspital, University of Bern , 3010 Bern, Switzerland.
  • 4 Institute of Pathology, University of Bern, 3008 Bern, Switzerland.
  • 5 Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, 3010, Bern, Switzerland.
  • 6 Institute of Pathology, University of Bern , 3008 Bern, Switzerland.
  • 7 Biozentrum, University of Basel, 4056 Basel, Switzerland.
PMID: 35583599 DOI: 10.1210/endocr/bqac076
Abstract

Adrenarche is an early event in sexual maturation in prepubertal children and corresponds to the postnatal development of the adrenocortical zona reticularis (zR). However, 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 with other adrenal layers. To model this metabolic condition, we challenged adrenal cells in vitro using Cholesterol deprivation. This resulted in reprogramming the steroidogenic pathway toward inactivation of 3-beta-hydroxysteroid dehydrogenase type 2 (HSD3B2), increased CYB5A expression, and increased biosynthesis of dehydroepiandrosterone (DHEA), 3 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.

Keywords

DHEA; adrenarche; cholesterol.

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