Effects of ketoconazole on progesterone and cAMP production in MA-10 mouse Leydig tumor cells.
The effects of ketoconazole (KCZ) on secretion of progesterone and cAMP in Leydig cells were investigated in vitro. MA-10 mouse Leydig tumor cells were used to conduct the experiments. KCZ significantly inhibited the progesterone production from MA-10 cells in a dose dependent fashion between 2 and 20 microM among 1, 2 and 3 h of incubation. There was a statistically significant difference in luteinizing hormone (LH) stimulated progesterone production inhibited by 2 and 20 microm KCZ treatment compared to the control. The effect of KCZ on progesterone biosynthesis in MA-10 cells was mediated by cAMP, since KCZ suppressed basal and LH stimulated cAMP production and content within the same dose range. The stimulatory effects of forskolin and sodium fluoride on the adenylate cyclase system were also inhibited by KCZ. Moreover, dibutyryl cAMP blocked the inhibitory effect on steroidogenesis of KCZ in MA-10 cells. These data indicated that KCZ induced the inhibition of a catalytic component of adenylate cyclase holoenzyme in MA-10 mouse Leydig tumor cells.
Chang
Cicero Lee-Tian
CL
Department of Veterinary Medicine, College of Veterinary Medicine, National Chang Hsing University, Taichung, Taiwan, ROC. d8538002@mail.nchu.edu.tw
Fung
Hang-Poung
HP
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D003994:Bucladesine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D007654:Ketoconazole / Q000494:pharmacology*; D007700:Kinetics; D007986:Luteinizing Hormone / Q000494:pharmacology; D008297:Male; D051379:Mice; D011374:Progesterone / Q000096:biosynthesis*; D018310:Sertoli-Leydig Cell Tumor / Q000378:metabolism*; D012969:Sodium Fluoride / Q000494:pharmacology; D013736:Testicular Neoplasms / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000935:Antifungal Agents; D005576:Colforsin; D011374:Progesterone; D003994:Bucladesine; D012969:Sodium Fluoride; D007986:Luteinizing Hormone; D000242:Cyclic AMP; D007654:Ketoconazole