Related Experiment Video
Updated: Aug 10, 2026
Mouse Adrenal Chromaffin Cell Isolation
Published on: January 5, 2007
Cytotoxic drugs and the human adrenal cortex: a cell culture study
Abstract:
Primary monolayer cultures of nonproliferating adult human adrenocortical cells have been used to screen 18 cytotoxic drugs used in cancer chemotherapy for direct effects on corticosteroidogenesis. None of the drugs tested, with the exception of 5-fluorouracil (5-FU) and its metabolite 5-fluorodeoxyuridine, showed significant activity at levels compatible with cortical cell viability and/or likely to be encountered during therapy. These two antimetabolites, however, resulted in a slow but long-lived reversible suppression of corticosteroidogenesis in both ACTH- and monobutyryl cyclic AMP-stimulated, as well as unstimulated cultures of human cells. Thus 10 micrograms/ml resulted in less than 80% inhibition after seven days treatment without any evidence of overt cytotoxicity. High-pressure liquid chromatography showed a suppression of all UV-absorbing steroids secreted. Examination of the ultrastructure of the treated cells showed significant changes in mitochondrial morphology, suggesting a possible site of action for the antisteroidogenic effects of 5-fluorouracil. These in vitro results suggest the possibility of adrenal suppression in vivo during long-term or high dose infusion 5-FU chemotherapy.
Insights
Cancer drug 5-fluorouracil (5-FU) can suppress adrenal function by affecting corticosteroidogenesis. This study found 5-FU reversibly inhibits steroid production in human adrenocortical cells, suggesting potential adrenal suppression during chemotherapy.
Area of Science:
- Endocrinology
- Pharmacology
- Cell Biology
Background:
- Cancer chemotherapy utilizes cytotoxic drugs to eliminate rapidly dividing cells.
- Adrenocortical cells are responsible for producing vital corticosteroids.
- The direct impact of chemotherapy agents on corticosteroidogenesis is not fully understood.
Purpose of the Study:
- To screen cytotoxic anticancer drugs for direct effects on corticosteroidogenesis in human adrenocortical cells.
- To investigate the specific effects of 5-fluorouracil (5-FU) on steroid production and cellular structure.
Main Methods:
- Primary monolayer cultures of nonproliferating adult human adrenocortical cells were used.
- Eighteen cytotoxic drugs were screened for their effects on corticosteroidogenesis.
- High-pressure liquid chromatography and ultrastructural examination were employed to analyze steroid production and cell morphology.
Main Results:
- Most tested drugs showed no significant activity on corticosteroidogenesis at therapeutic levels.
- 5-fluorouracil (5-FU) and 5-fluorodeoxyuridine caused a slow, long-lived, reversible suppression of corticosteroidogenesis.
- 5-FU treatment led to significant changes in mitochondrial morphology without overt cytotoxicity.
Conclusions:
- 5-FU and its metabolite exhibit antisteroidogenic effects on human adrenocortical cells in vitro.
- Mitochondrial morphology changes suggest a potential mechanism for 5-FU's effect on steroidogenesis.
- These findings indicate a possibility of in vivo adrenal suppression during 5-FU chemotherapy.
