Nicotinamide Nucleotide Transhydrogenase Is Essential for Adrenal Steroidogenesis: Clinical and In Vitro Lessons
Authors' conclusion
Together, these studies demonstrate the essential role of NNT in adrenal redox homeostasis and steroidogenesis.
Study context
- Population
- A boy with familial glucocorticoid deficiency (FGD) with a novel NNT variant; H295R adrenocortical carcinoma cells; fetal and postnatal human adrenals
- Comparison
- NNT p.G866D homozygous or NNT knockdown cells vs wild-type (WT) NNT cells
- Outcome
- Role of NNT in redox homeostasis and steroidogenesis
Methodological detailscase report with genotype-phenotype evaluation, in vitro, CRISPR/Cas9 knockdown model, immunohistochemistry
- Case report with genotype-phenotype evaluation
- In vitro
- CRISPR/Cas9 knockdown model
- Immunohistochemistry
Main finding
As reported in the abstract
- Homozygous NNT p.G866D variant segregated with the FGD phenotype
- p.G866D cells (basal and oxidative stress (OS) conditions): increased ROS production, decreased GSH and mitochondrial mass vs WT
- NNT knockdown H295R cells: impaired NNT protein expression, increased ROS production, decreased mitochondrial mass and size and density of cholesterol lipid droplets
- NNT knockdown affected steroidogenic enzyme expression, impairing cortisol and aldosterone secretion
- NNT abundantly expressed in the transition fetal zone and zona fasciculata of human adrenals
Original publication
Nicotinamide Nucleotide Transhydrogenase Is Essential for Adrenal Steroidogenesis: Clinical and In Vitro Lessons. J Clin Endocrinol Metab. Published 7 December 2022. doi:10.
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