Kinetic analysis of steroid 5alpha-reductase activity at neutral pH in benign prostatic hyperplastic tissue: evidence for type I isozyme activity in the human prostate.
In human benign prostatic hyperplastic (BPH) tissue homogenates 5alpha-reduction of testosterone was examined at neutral pH. As Lineweaver-Burk and Eadie-Scatchard plots of estimated initial velocities against a wide range of substrate concentrations of 2 nM to 3.2 microM were non-linear, the existence of two 5alpha-reductase isozymes in this tissue was surmised. Indeed, enzyme parameters at pH 7.0 suggested the presence of two isozymes with affinity constants of 1995 and 11.8 nM, characteristic of the well established human steroid 5alpha-reductase isozymes type I and II, respectively. The physiological roles of these isozyme activities remain puzzling. The specific activities, Vmax, of these subtypes indicated an approx. 6-fold higher maximum velocity of type I than of type II 5alpha-reductase in the human hyperplastic prostate at this pH. In contrast, the efficiency ratios, Vmax/Km, demonstrated that the type II isozyme had a nearly 27 times higher potential in vivo activity than the type I isozyme, and is therefore most probably quantitatively responsible for dihydrotestosterone formation at physiological testosterone levels in this tissue at neutral pH. This is the first full paper on type I 5alpha-reductase activity in human BPH tissue.
Span
P N
PN
Department of Medicine, Division of Endocrinology, University Hospital Nijmegen, The Netherlands.
Benraad ThJ
Sweep
C G
CG
Smals
A G
AG
D000368:Aged; D042944:Cholestenone 5 alpha-Reductase; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007527:Isoenzymes / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010088:Oxidoreductases / Q000737:chemistry / Q000378:metabolism*; D011470:Prostatic Hyperplasia / Q000201:enzymology* / Q000378:metabolism; D015203:Reproducibility of Results; D014020:Tissue Extracts / Q000737:chemistry / Q000378:metabolism
D007527:Isoenzymes; D014020:Tissue Extracts; D010088:Oxidoreductases; D042944:Cholestenone 5 alpha-Reductase