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Ketoconazole inhibits corticotropic cell function in vitro.
G K Stalla1, J Stalla, M Huber
1Department of Internal Medicine, University of Munich, West Germany.
Endocrinology
|February 1, 1988
Summary
Ketoconazole inhibits adrenocorticotropic hormone (ACTH) release and biosynthesis by blocking adenylate cyclase activity in rat pituitary cells. This effect is reversible and mediated through cyclic AMP (cAMP) pathways.
Area of Science:
- Endocrinology
- Molecular Pharmacology
Background:
- Adrenocorticotropic hormone (ACTH) plays a crucial role in the stress response and adrenal function.
- Understanding the regulation of ACTH secretion and biosynthesis is vital for managing endocrine disorders.
Purpose of the Study:
- To investigate the in vitro effects of ketoconazole (KC) on ACTH secretion and biosynthesis.
- To elucidate the mechanism by which KC influences ACTH production and cyclic AMP (cAMP) generation in rat anterior pituitary cells.
Main Methods:
- Primary cultures and pituitary fragments from rats were utilized.
- Cells were treated with varying concentrations of ketoconazole (KC) in the presence or absence of corticotropin-releasing factor (CRF).
- ACTH release, biosynthesis (mRNA levels), and intracellular cAMP levels were measured.
Main Results:
- Ketoconazole (KC) inhibited corticotropin-releasing factor (CRF)-stimulated ACTH release in a dose-dependent manner.
- KC also reduced basal and CRF-stimulated ACTH biosynthesis and mRNA levels.
- KC dose-dependently inhibited both basal and CRF-stimulated cAMP release and content, suggesting a role for cAMP in mediating KC's effects.
Conclusions:
- Ketoconazole (KC) inhibits ACTH secretion and biosynthesis in rat anterior pituitary cells.
- The mechanism involves the inhibition of the catalytic component of adenylate cyclase, leading to reduced cAMP levels.
- These inhibitory effects of KC on ACTH production are reversible upon removal of the drug.