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- W2024142431 abstract "To determine the antisteroidogenic effect of ketoconazole (KTZ) in the human testis, we measured the plasma Δ5-pregnenolone, Δ5-17α-hydroxypregnenolone, dehydroepiandrosterone (DHEA), progesterone, 17α-hydroxyprogesterone, androstenedione (A), and testosterone (T) concentrations in three men with previously untreated metastatic prostate cancer at various time intervals for 24 h before and 48 h after the administration of 200 mg oral KTZ every 8 h. The adrenal glands of these three patients were suppressed (as measured by the plasma cortisol levels) by the administrátion of 1.0 mg dexamethasone daily for 7 days before and during the study. After six doses of KTZ, bilateral orchiectomy was performed, and the intratesticular concentration of the aforementioned seven steroids and the intratesticular activities of the 17α-hydroxylase, 17,20-desmolase, and 17β-hydroxysteroid dehydrogehase enzymes in the Δ4-steroidogenic pathway were determined. These seven intratesticular steroids and three intratesticular enzyme activities were compared to those in five men with previously untreated prostate cancer who underwent orchiectomy as primary treatment for their disease. Plasma A, DHEA, and T all significantly decreased during KTZ therapy. There was no significant change in the other four steroids in the plasma. In the testis, Δ5-pregnenolone, Δ5-17α-hydroxypregnenolone, and Δ4-17α-hydroxyprogesterone were all significantly elevated, whereas intratesticular DHEA, A, and T were significantly decreased in the three KTZ-treated patients compared to levels in the five non-KTZ-treated patients. Measurement of the enzyme activities demonstrated a significant reduction in both 17α-hydroxylase and 17,20-desmolase, but no change in 17β-hydroxysteroid dehydrogenase, in the KTZ-treated patients compared to the levels in the non-KTZ-treated patients. We conclude that oral KTZ decreases testicular T production by inhibiting the 17,20-desmolase and also the 17α-hydroxylase steps in both the Δ4- and Δ6-T biosynthetic pathways." @default.
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- W2024142431 date "1986-11-01" @default.
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- W2024142431 title "Mechanism of Inhibition of Human Testicular Steroidogenesis by Oral Ketoconazole∗" @default.
- W2024142431 doi "https://doi.org/10.1210/jcem-63-5-1193" @default.
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