Identification and partial characterization of two steroid 5α-reductase isozymes in the canine prostate

✍ Scribed by Span, Paul N.; Schalken, Jack A.; Sweep, Fred G.J.; Smals, Anthony G.H.

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 123 KB
• Volume: 34
• Category: Article
• ISSN: 0270-4137
• DOI: 10.1002/(sici)1097-0045(19980215)34:3<222::aid-pros10>3.0.co;2-g

✦ Synopsis

BACKGROUND.

The dog has been extensively used as an in vivo model to test the pharmacokinetics and effects on pathological prostatic growth of 5␣-reductase inhibitors. However, no information is available on the existence or characteristics of canine 5␣-reductase isozymes. METHODS. The 5␣-reduction of testosterone is analyzed in dog prostatic homogenates. Three human-specific inhibitors are tested for their activity against dog 5␣-reductase. RESULTS. Two pH optima of 5␣-reductase activity in dog prostatic homogenates are described, comparable to the pH optima of rat and human 5␣-reductase isozymes. Kinetic analysis of 5␣-reductase enzymatic activity at pH 7.0 revealed isozymes with a low apparent affinity constant (K m = 2.67 nM) and a high apparent affinity constant (K m = 1.23 M). These apparent affinity constants compare favorably to the human and rat isozymes types II and I, respectively. The human type II inhibitor finasteride selectively inhibited the low K m isozyme, whereas the human type I inhibitor MK386 preferentially inhibited the high K m isozyme. The human type I inhibitor LY306089 was nonspecific for the dog isozymes. CONCLUSIONS. We postulate that the high and low K m isozymes described here represent the dog type I and type II 5␣-reductase isozymes, respectively.