Comparative study of human steroid 5alpha-reductase isoforms in prostate and female breast skin tissues: sensitivity to inhibition by finasteride and epristeride.
Steroid 5alpha-reductase (5-AR) catalyses the reduction of testosterone (T) to dihydrotestosterone (DHT). The 5alpha-reductase found in human benign prostatic hyperplasia (BPH) has been compared with that found in human breast skin tissue in respect of sensitivity to inhibition by Finasteride and Epristeride. Kinetic studies showed the presence of two isoforms of 5alpha-reductase in benign prostatic hyperplasia indicated by low and high Km isoforms for testosterone, while female breast skin tissue contained only one isoform. The isoforms differ in their affinity for the inhibitors Finasteride and Epristeride, both compounds being more effective for the low Km 5alpha-reductase isoform than the high Km 5alpha-reductase of prostatic tissue, with Finasteride displaying competitive inhibition and Epristeride uncompetitive. Finasteride and Epristeride are also inhibitors of skin 5alpha-reductase, which possesses a comparable Ki for Finasteride to that of the low Km prostatic enzyme, but Epristeride was a less potent inhibitor of the skin enzyme relative to the prostate isoform. These results suggest that the inhibitors have therapeutic potential, other than for treatment of benign prostatic hyperplasia, for treating skin disorders influenced by the action of dihydrotestosterone and warrant further investigation.
Ranjan
Mala
M
Biochemistry Group, School of Biological Sciences, Wallace Building, University of Wales Swansea, Singleton Park, Swansea SA2 8PP, United Kingdom.
Diffley
Penny
P
Stephen
Gita
G
Price
David
D
Walton
Terence J
TJ
Newton
Russell P
RP
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D058891:5-alpha Reductase Inhibitors; D000730:Androstadienes / Q000494:pharmacology*; D001940:Breast / Q000187:drug effects* / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D018120:Finasteride / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000187:drug effects* / Q000201:enzymology
D058891:5-alpha Reductase Inhibitors; D000730:Androstadienes; D004791:Enzyme Inhibitors; D007527:Isoenzymes; C072547:epristeride; D018120:Finasteride; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase