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Mitotane reduces human and mouse ACTH-secreting pituitary cell viability and function
Erica Gentilin1, Federico Tagliati, Massimo Terzolo
1Section of Endocrinology, Department of Medical Sciences, University of Ferrara, Via Savonarola 9, 44100 Ferrara, Italy.
The Journal of Endocrinology
|July 2, 2013
Summary
Mitotane, used for Cushing's disease (CD), directly impacts pituitary corticotroph cells. This study shows mitotane reduces cell viability and ACTH secretion, suggesting direct pituitary effects.
Area of Science:
- Endocrinology
- Molecular Biology
- Oncology
Background:
- Cushing's disease (CD) treatment primarily targets adrenal function.
- Pituitary-directed therapies for CD show limited efficacy.
- Mitotane's direct effects on pituitary corticotrophs in CD remain unclear.
Purpose of the Study:
- To investigate mitotane's effects on corticotroph function and survival.
- To examine mitotane's impact on mouse pituitary cell line (AtT20/D16v-F2) and human pituitary adenoma cells.
Main Methods:
- Utilized AtT20/D16v-F2 mouse pituitary cell line.
- Employed primary cultures of human ACTH-secreting pituitary adenomas.
- Assessed cell viability, apoptosis, ACTH secretion, and Pomc expression.
Main Results:
- Mitotane reduced cell viability via caspase-mediated apoptosis in both cell models.
- Mitotane decreased ACTH secretion and Pomc expression.
- Mitotane blocked corticotropin-releasing hormone stimulation of viability, ACTH secretion, and Pomc expression.
Conclusions:
- Mitotane exerts direct effects on the viability and function of ACTH-secreting pituitary adenoma cells.
- These findings suggest a direct pituitary action of mitotane on corticotroph cells.
- Mitotane's pituitary effects occur at doses within the therapeutic range for certain conditions.
