Effects of topical antiandrogen and 5-alpha-reductase inhibitors on sebaceous glands in male fuzzy rats.
The fuzzy rat, a genetic mutant between hairless and hairy albino rats, expresses androgen-dependent hypersecretion of sebum and hyperplastic sebaceous glands. Using this model for human acne, we examined the effects of inhibitors of human steroid 5 alpha-reductase isozymes, type I (MK 386) and type II (finasteride), and an androgen receptor blocker (RU58841) on regression of glandular and ductal hyperplasia. The above three agents, 1% weight volume, were dissolved into the vehicle (propylene glycol, alcohol and water) and applied on the backs of peripubertal male rats for 2 months. Control and castrate groups received vehicle alone. At 8 weeks, we examined the size the sebaceous glandular lobules and ducts in split epidermal preparations as well as in frozen sections of skin stained with osmium-potassium dichromate solution. The number of bromodeoxyuridine (BrdU)-positive cells was counted in the glandular lobes in split-skin tissues stained with BrdU immunochemistry. The results revealed that the sizes of both lobes and ducts in castrates were 40-60% smaller than in controls. RU58841 induced glandular and ductal regression equivalent to that in castrates. Finasteride induced a moderate degree of lobular and ductal reduction, whereas MK386 caused only ductal regression. Reduction of BrdU-positive cells in the sebaceous lobes was found in the skin treated with finasteride and RU58841. Serum concentrations of testosterone and dihydrotestosterone showed no significant changes in all drug-treated rats. The weight of the prostatic lobes was reduced significantly in rats treated with finasteride but not by the other two agents. RU58841 effectively counteracted endogenous androgens resulting in a suppression of growth of the sebaceous glands but not the prostate. This rodent model for androgen-dependent hyperplasia of the sebaceous glands is useful for the study of many pharmacological aspects comprising the rate of percutaneous absorption, stability and affinity to target organs of the testing compounds, and selection of adequate vehicle for topical application.
Ye
F
F
Wisconsin Regional Primate Research Center, University of Wisconsin, Madison 53715-1299, USA.
Imamura
K
K
Imanishi
N
N
Rhodes
L
L
Uno
H
H
D058891:5-alpha Reductase Inhibitors; D000284:Administration, Oral; D000726:Androgen Antagonists / Q000494:pharmacology*; D000818:Animals; D001973:Bromodeoxyuridine / Q000032:analysis; D012628:Dermatitis, Seborrheic / Q000188:drug therapy / Q000201:enzymology; D013196:Dihydrotestosterone / Q000097:blood; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011922:Rats, Mutant Strains; D012627:Sebaceous Glands / Q000033:anatomy & histology / Q000187:drug effects*; D013739:Testosterone / Q000097:blood
D058891:5-alpha Reductase Inhibitors; D000726:Androgen Antagonists; D004791:Enzyme Inhibitors; D013196:Dihydrotestosterone; D013739:Testosterone; D001973:Bromodeoxyuridine