Summary
Cyproterone acetate, R 2956, Ro 7-2340 and Sch 13521 in the daily dose of 8 mg injected intramuscularly to castrated adult hamsters for 3 weeks were all found to significantly antagonize the stimulatory effect of exogenous testosterone propionate (80 μg im, every other day) on the sebaceous gland as well as the prostate and the seminal vesicle. With a view to clarifying the mechanisms of action of these antiandrogenic drugs on the sebaceous gland, the present author carried out both in vivo and in vitro experiments and examined how they would interfere with the binding of 3H-dihydrotestosterone (DHT) to cytosol and nuclei. When 200–1000 excess quantities of the antiandrogens were administered to the experimental animals 10 min before injection of 3H-testosterone, all of them except R 2956 reduced the bound radioactivity in the nuclei of the sebaceous gland by more than 40%. Incubation of the cytosol fraction with 1×10-7 M of cyproterone acetate caused a 70% decrease in radioactivity of the specific binding. In contrast, such inhibitory activities of the three other antiandrogens were less conspicuous even at 1×10-6 M. In the homogenate of the sebaceous gland incubated with 1×10-8 M of DHT, the other drugs than Sch 13521 curbed the characteristic binding of DHT to macromolecules of the nuclei by nearly 70% at 1×10-6 M.
Zusammenfassung
Cyproteronacetat, R 2956, Ro 7-2340 und Sch 13521, welches täglich in einer Dosis von 8 mg intramuskulär kastrierten erwachsenen Hamstern über 3 Wochen injiziert wurde, verminderten signifikant den stimulierenden Effekt vom intramuskulär verabfolgten Testosteronpräparat. Die untersuchten Parameter waren die Talgdrüsen, die Prostata und die Samenbläschen. Um den Wirkungsnachweis aufzuklären, wurden in vivo- und in vitro-Untersuchungen darüber angestellt, inwieweit die Bindung von Dihydrotestosteron an Cytosol und Kernen beeinträchtigt wird. Bei Gabe von Antiandrogenen 10 min vor der Injektion von Testosteron wurde bei allen Präparaten, mit Ausnahme von R 2956 die kerngebundene Radioaktivität in den Talgdrüsen mehr als 40% vermindert. Die Inkubation der Cytosolfraktion mit 10-7 M Cyproteronacetat bewirkte eine 70% ige Abnahme der spezifischen Bindung. Die inhibierten Aktivitäten von drei anderen Antiandrogenen waren sogar bei 10-6 M weniger auffällig. Im Homogenat der Talgdrüse, welche mit 10-8 M DHT inkubiert wurde, konnten alle Medikamente mit Ausnahme von Sch 13521 die Bindungsfähigkeit von DHT an Makromoleküle der Kerne auf nahezu 70% bei 10-6 M begrenzen.
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Abbreviations
- 6-chloro-17α-hydroxy-1α:
-
2α-methylelene-4,6-pregnadiene-3,20-dione-17-acetate
- R 2956:
-
17β-hydroxy-2,2,7α-trimethylestra-4,9,11-triene-3-one
- Ro 7-2340:
-
6α-bromo-17β-hydroxy-17α-methyl-4-oxa-5α-androstane-3-one
- Sch 13521:
-
α,α,α-trifluoro-2-methyl-4′-nitro-m-propionotoluidide
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Takayasu, S. Effect of antiandrogens on the binding of androgen to cytosol and nuclei of hamster sebaceous glands. Arch Dermatol Res 264, 49–54 (1979). https://doi.org/10.1007/BF00417278
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DOI: https://doi.org/10.1007/BF00417278