Growth Suppression of Hamster Flank Organs by Topical Application of γ-Linolenic and Other Fatty Acid Inhibitors of 5α-Reductase

Certain unsaturated aliphatic fatty acids, such as γ-linolenic acid, inhibit 5α-reductase activity in vitro and in vivo. Hamster flank organ growth, as measured by the increase in the area of pigmented macule, is dependent on androgen. When one of the paired flank organs of a castrated hamster was treated topically with testosterone, the treated organ, but not the contralateral flank organ, became larger and darker. Topical application of γ-linolenic acid to the testosterone-treated flank organ suppressed this testosterone effect. Other fatty acids that were not inhibitors of 5α-reductases were not active. Topical treatment of hamster flank organs with 5α-dihydrotestosterone also stimulated the growth of the organ. This 5α-dihydrotestosterone-dependent activity, however, was not significantly affected by γ-linolenic acid, suggesting that flank organ growth was dependent on 5α-dihydrotestosterone and that γ-Iinolenic acid acted by inhibiting 5α-reductase. With intact male hamsters, the endogenous androgen-dependent growth of flank organs is also suppressed by topical treatment with γ-linolenic acid. The effect of γ-linolenic acid is localized at the site of its application; topical application of γ-Iinolenic acid did not affect the androgen-dependent growth of other organs such as testis, epididymis, seminal vesicle, and prostate. γ-Linolenic acid, with low toxicity and absence of systemic effect, therefore may be potentially useful for treatment of androgen-dependent skin disorders.