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Hassan, Hassan Ali; El-Gezeiry, Dalal; Nafaa, Tamer M.; Baghdady, Iman

doi:10.1023/a:1013165006406

Cited by 12 publications

(2 citation statements)

References 34 publications

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“…For example, we and others have previously found that administration of a low dose of KCZ to polycystic ovarian syndrome patients during superovulation attenuated ovarian folliculogenesis8,9 and better controlled the hyperstimulated response to gonadotropins 8. In addition, KCZ was also shown to improve clomiphene responsiveness in PCOS patients 10. In view of the potentially beneficial use of KCZ in reproduction, several studies attempted to analyze the biochemical basis for the drug effect on the ovary 8,11–18.…”

Section: Introductionmentioning

confidence: 99%

“… 8 In addition, KCZ was also shown to improve clomiphene responsiveness in PCOS patients. 10 In view of the potentially beneficial use of KCZ in reproduction, several studies attempted to analyze the biochemical basis for the drug effect on the ovary. 8 , 11 – 18 However, the use of multiple experimental models yielded incomplete and occasionally contradictory information that led us to seek a model providing a complete view of the drug effects on the entire ovarian steroidogenic enzymatic cascade starting from cholesterol down to estradiol synthesis.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Selective Inhibition of Steroidogenic Enzymes by Ketoconazole in Rat Ovary Cells

Gal

Orly

2014

Clin Med�Insights�Reprod�Health

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OBJECTIVEKetoconazole (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.METHODSFollowing 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).RESULTSKCZ 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-Δ5–4 isomerase type 1 (3βHSD1), 5α-reductase, 20α-hydroxysteroid dehydrogenase (20α-HSD), 3α-hydroxysteroid dehydrogenase (3α-HSD), and 17β-hydroxysteroid dehydrogenase type 1 (17HSD1).CONCLUSIONThese 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.

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