Search Results
You are looking at 1 - 1 of 1 items for
- Author: F H de Jong x
- Refine by access: Content accessible to me x
Search for other papers by R van der Pas in
Google Scholar
PubMed
Search for other papers by L J Hofland in
Google Scholar
PubMed
Search for other papers by J Hofland in
Google Scholar
PubMed
Search for other papers by A E Taylor in
Google Scholar
PubMed
Search for other papers by W Arlt in
Google Scholar
PubMed
Search for other papers by J Steenbergen in
Google Scholar
PubMed
Search for other papers by P M van Koetsveld in
Google Scholar
PubMed
Search for other papers by W W de Herder in
Google Scholar
PubMed
Search for other papers by F H de Jong in
Google Scholar
PubMed
Search for other papers by R A Feelders in
Google Scholar
PubMed
The antifungal agent ketoconazole is often used to suppress cortisol production in patients with Cushing's syndrome (CS). However, ketoconazole has serious side effects and is hepatotoxic. Here, the in vitro effects of ketoconazole and fluconazole, which might be less toxic, on human adrenocortical steroidogenesis were compared. The effects on steroidogenesis were examined in primary cultures of nine human adrenocortical tissues and two human adrenocortical carcinoma cell lines. Moreover, the effects on mRNA expression levels of steroidogenic enzymes and cell growth were assessed. Ketoconazole significantly inhibited 11-deoxycortisol (H295R cells; maximum inhibition 99%; EC50 0.73 μM) and cortisol production (HAC15 cells; 81%; EC50 0.26 μM and primary cultures (mean EC50 0.75 μM)). In cultures of normal adrenal cells, ketoconazole increased pregnenolone, progesterone, and deoxycorticosterone levels, while concentrations of 17-hydroxypregnenolone, 17-hydroxyprogesterone, 11-deoxycortisol, DHEA, and androstenedione decreased. Fluconazole also inhibited 11-deoxycortisol production in H295R cells (47%; only at 1 mM) and cortisol production in HAC15 cells (maximum inhibition 55%; EC50 35 μM) and primary cultures (mean EC50 67.7 μM). In the cultures of normal adrenals, fluconazole suppressed corticosterone, 17-hydroxypregnenolone, and androstenedione levels, whereas concentrations of progesterone, deoxycorticosterone, and 11-deoxycortisol increased. Fluconazole (1 mM) slightly increased STAR mRNA expression in both cell lines. Neither compound affected mRNA levels of other steroidogenic enzymes or cell number. In conclusion, by inhibiting 11β-hydroxylase and 17-hydroxylase activity, pharmacological concentrations of fluconazole dose dependently inhibit cortisol production in human adrenocortical cells in vitro. Although fluconazole seems less potent than ketoconazole, it might become an alternative for ketoconazole to control hypercortisolism in CS. Furthermore, patients receiving fluconazole because of mycosis might be at risk for developing adrenocortical insufficiency.