Mitochondrial dysfunction results in enhanced adrenal androgen production in H295R cells.
J Steroid Biochem Mol Biol
; 243: 106561, 2024 Oct.
Article
em En
| MEDLINE
| ID: mdl-38866189
ABSTRACT
The role of mitochondria in steroidogenesis is well established. However, the specific effects of mitochondrial dysfunction on androgen synthesis are not fully understood. In this study, we investigate the effects of various mitochondrial and metabolic inhibitors in H295R adrenal cells and perform a comprehensive analysis of steroid and metabolite profiling. We report that mitochondrial complex I inhibition by rotenone shifts cells toward anaerobic metabolism with a concomitant hyperandrogenic phenotype characterized by rapid stimulation of dehydroepiandrosterone (DHEA, 2â¯h) and slower accumulation of androstenedione and testosterone (24â¯h). Screening of metabolic inhibitors confirmed DHEA stimulation, which included mitochondrial complex III and mitochondrial pyruvate carrier inhibition. Metabolomic studies revealed truncated tricarboxylic acid cycle with an inverse correlation between citric acid and DHEA production as a common metabolic marker of hyperandrogenic inhibitors. The current study sheds light on a direct interplay between energy metabolism and androgen biosynthesis that could be further explored to identify novel molecular targets for efficient treatment of androgen excess disorders.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Desidroepiandrosterona
/
Androgênios
/
Mitocôndrias
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article