Local and systemic reduction by topical finasteride or flutamide of hamster flank organ size and enzyme activity.
The hamster flank organ is a widely used model of the control of sebaceous gland activity by androgens and anti-androgens. Finasteride, a 5 alpha-reductase inhibitor, was administered locally on the surface of the right flank organ and right ear twice daily for 4 weeks. The treatment caused similar 12% to 30% reductions in the size of the sebaceous glands in both flank organs. Moreover, relative mRNA levels of the androgen-regulated FAR-17a gene measured by in situ hybridization as well as [3H]-thymidine incorporation and 5 alpha-reductase activity were similarly decreased in the two flank organs after topical application. The pure anti-androgen flutamide, at the same doses, exerted a more potent effect on all the same parameters, and the effect was also comparable on both the treated and untreated sides of flank organs. Finasteride and flutamide significantly decreased ventral and dorsal prostatic weights after topical application. The present data show that the topical administration of finasteride, in analogy with flutamide, causes local inhibition of sebaceous gland growth in both the costovertebral organs and ears. However, as demonstrated by the similar inhibitory effect in the contralateral untreated side and the reduced weight of the dorsal and ventral lobes of the prostate and seminal vesicles, finasteride and flutamide both exert significant systemic effects.
Chen
C
C
MRC Group in Molecular Endocrinology, CHUL Research Center, Québec, Canada.
Puy
L A
LA
Simard
J
J
Li
X
X
Singh
S M
SM
Labrie
F
F
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism*; D058891:5-alpha Reductase Inhibitors; D000287:Administration, Topical; D000726:Androgen Antagonists / Q000008:administration & dosage; D000818:Animals; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004423:Ear; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D018120:Finasteride / Q000008:administration & dosage*; D005485:Flutamide / Q000008:administration & dosage*; D017403:In Situ Hybridization; D008297:Male; D008647:Mesocricetus; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D012627:Sebaceous Glands / Q000033:anatomy & histology / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D058891:5-alpha Reductase Inhibitors; D000726:Androgen Antagonists; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D014316:Tritium; D018120:Finasteride; D005485:Flutamide; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; D013936:Thymidine