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The Antiandrogenic Action of 4–Androsten–3–one–17β– Carboxylic Acid and Its Methyl Ester on Hamster Flank Organ¹

Departments of Dermatology and Biochemistry, University of Miami School of Medicine Miami, Florida 33136

Abstract

4–Androsten–3–one–17β–carboxylic acid (17βC), an inhibitor of testosterone 5–reductase, as discovered in our enzymic studies of human skin, was tested for its antiandrogenic potency in the hamster flank organ, which is an androgen—dependent sebaceous structure. The organ in the female animals enlarged in size and increased in pigmentation after topical application of testosterone propionate, 4 µg per day for 2 to 3 weeks. This response was completely inhibited by the concomitant application of 17βC or its methyl ester (400 µg per day). Topical application of 5–dihydrotestosterone (DHT, 4 jig per day) also caused the enlargement of the flank organ, but the action of DHT was not inhibited by 17βC. Incubation of [¹⁴C] testosterone with homogenates of the flank organ produced DHT and androstane–3,17β–diol (ADIOL) as the major metabolites. The formation of these two 5asteroids was inhibited by 17βC added in the incubation medium. These results indicate that 17βC is an antiandrogen, which acts by inhibition of the formation of DHT from testosterone, and suggest that when topically applied, this compound or its derivative may be useful in suppressing the excessive manifestation of androgen action, e.g., in skin disorders such as acne or seborrhea. (Endocrinology 92: 1216, 1973)

Footnotes

¹ 1This research was supported by Grants CA– 12990 and AM–09497 from the USPHS, and Grant F71–UM4 from the American Cancer Society, Florida Division.

Received October 2, 1972.

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