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• W2023266329 endingPage "CMRH.S14036" @default.
• W2023266329 startingPage "CMRH.S14036" @default.
• W2023266329 abstract "Ketoconazole (KCZ) is an anti-fungal agent extensively used for clinical applications related to its inhibitory effects on adrenal and testicular steroidogenesis. Much less information is available on the effects of KCZ on synthesis of steroid hormones in the ovary. The present study aimed to characterize the in situ effects of KCZ on steroidogenic enzymes in primary rat ovary cells.Following the induction of folliculogenesis in gonadotropin treated rats, freshly prepared ovarian cells were incubated in suspension for up to four hours while radiolabeled steroid substrates were added and time dependent generation of their metabolic products was analyzed by thin layer chromatography (TLC).KCZ inhibits the P450 steroidogenic enzymes in a selective and dose dependent manner, including cholesterol side-chain cleavage cytochrome P450 (CYP11A1/P450scc), the 17α-hydroxylase activity of CYP17A1/P450c17, and CYP19A1/P450arom, with IC50 values of 0.3, 1.8, and 0.3 μg/mL (0.56, 3.36, and 0.56 μM), respectively. Unaffected by KCZ, at 10 μg/mL, were the 17,20 lyase activity of CYP17A1, as well as five non-cytochrome steroidogenic enzymes including 3β-hydroxysteroid dehydrogenase-Δ(5-4) isomerase type 1 (3βHSD1), 5α-reductase, 20α-hydroxysteroid dehydrogenase (20α-HSD), 3α-hydroxysteroid dehydrogenase (3α-HSD), and 17β-hydroxysteroid dehydrogenase type 1 (17HSD1).These findings map the effects of KCZ on the ovarian pathways of progestin, androgen, and estrogen synthesis. Hence, the drug may have a potential use as an acute and reversible modulator of ovarian steroidogenesis in pathological circumstances." @default.
• W2023266329 created "2016-06-24" @default.
• W2023266329 creator A5009482668 @default.
• W2023266329 creator A5061267007 @default.
• W2023266329 date "2014-01-01" @default.
• W2023266329 modified "2023-10-16" @default.
• W2023266329 title "Selective Inhibition of Steroidogenic Enzymes by Ketoconazole in Rat Ovary Cells" @default.
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• W2023266329 doi "https://doi.org/10.4137/cmrh.s14036" @default.
• W2023266329 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4007567" @default.
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• W2023266329 hasPublicationYear "2014" @default.
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