Aminoglutethimide-induced lysosomal changes in adrenal gland in mice

Aminoglutethimide is a steroidogenesis inhibitor and inhibits a cholesterol side-chain cleavage enzyme (CYP11A1) that converts cholesterol to pregnenolone in mitochondria. We investigated histopathological changes induced by 5-day administration of AG in mice. Cytoplasmic vacuoles of various sizes a...

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Bibliographic Details
Published in:Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie 2017-09, Vol.69 (7), p.424-429
Main Authors: Mutsuga, Mayu, Asaoka, Yoshiji, Imura, Naoko, Miyoshi, Tomoya, Togashi, Yuko
Format: Article
Language:English
Subjects:
Adrenal Glands - drug effects
Adrenal Glands - pathology
Adrenal toxicity
Aminoglutethimide
Aminoglutethimide - toxicity
Animals
Aromatase Inhibitors - toxicity
Autophagy
Lysosomes - drug effects
Lysosomes - pathology
Male
Mice
Mouse
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Summary:Aminoglutethimide is a steroidogenesis inhibitor and inhibits a cholesterol side-chain cleavage enzyme (CYP11A1) that converts cholesterol to pregnenolone in mitochondria. We investigated histopathological changes induced by 5-day administration of AG in mice. Cytoplasmic vacuoles of various sizes and single cell necrosis were found in zona fasciculata cells in AG-treated mice. Some vacuoles were positive for adipophilin, whereas others were positive for lysosome-associated membrane protein-2 on immunohistochemical staining, indicating they were enlarged lipid droplets and lysosomes, respectively. Electron microscopy revealed enlarged lysosomes containing damaged mitochondria and lamellar bodies in zona fasciculata cells, and they were considered to reflect the intracellular protein degradation processes, mitophagy and lipophagy. From these results, we showed that AG induces excessive lipid accumulation and mitochondrial damage in zona fasciculata cells, which leads to an accelerated lysosomal degradation in mice.
ISSN:0940-2993
1618-1433
DOI:10.1016/j.etp.2017.04.004