Growth suppression of hamster flank organs by topical application of gamma-linolenic and other fatty acid inhibitors of 5alpha-reductase.
Certain unsaturated aliphatic fatty acids, such as gamma-linolenic acid, inhibit 5alpha-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 gamma-linolenic acid to the testosterone-treated flank organ suppressed this testosterone effect. Other fatty acids that were not inhibitors of 5alpha-reductases were not active. Topical treatment of hamster flank organs with 5alpha-dihydrotestosterone also stimulated the growth of the organ. This 5alpha-dihydrotestosterone-dependent activity, however, was not significantly affected by gamma-linolenic acid, suggesting that flank organ growth was dependent on 5alpha-dihydrotestosterone and that gamma-linolenic acid acted by inhibiting 5alpha-reductase. With intact male hamsters, the endogenous androgen-dependent growth of flank organs is also suppressed by topical treatment with gamma-linolenic acid. The effect of gamma-linolenic acid is localized at the site of its application; topical application of gamma-linolenic acid did not affect the androgen-dependent growth of other organs such as testis, epididymis, seminal vesicle, and prostate. gamma-Linolenic acid, with low toxicity and absence of systemic effect, therefore may be potentially useful for treatment of androgen-dependent skin disorders.
Liang
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Ben May Institute for Cancer Research and the Department of Biochemistry and Molecular Biology, University of Chicago, Illinois 60637, U.S.A.
Liao
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D000287:Administration, Topical; D000818:Animals; D042944:Cholestenone 5 alpha-Reductase; D006224:Cricetinae; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006128:Growth / Q000187:drug effects*; D008297:Male; D008647:Mesocricetus / Q000033:anatomy & histology*; D008954:Models, Biological; D009919:Orchiectomy; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D010858:Pigmentation / Q000187:drug effects; D012627:Sebaceous Glands / Q000502:physiology; D017965:gamma-Linolenic Acid / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D017965:gamma-Linolenic Acid; D010088:Oxidoreductases; D042944:Cholestenone 5 alpha-Reductase