Kinetic parameters (KM and Vmax) of the 5 alpha-reductase activities in homogenates of stroma and epithelium, isolated from BPH tissue, were determined using both testosterone and progesterone as substrate. The mean KM values for stromal 5 alpha-reductase, at 67.9 nM and 27.7 nM for testosterone and progesterone respectively, were 3-4-fold higher than the comparable KM estimates for the epithelial enzyme. The KM estimates for the epithelial 5 alpha-reductase showed little variation whereas those measured in the stromal homogenates could be subgrouped at less than 50 nM and greater than 100 nM. The mean Vmax for the stromal 5 alpha-reductase was approximately 235 pmol/30 min/mg protein irrespective of the substrate used; a value 10-fold higher than the Vmax of the epithelial 5 alpha-reductase. Preliminary experiments with inhibitors of 5 alpha-reductase demonstrated that the stromal and epithelial enzymes differed in their relative sensitivity to these compounds. Three major conclusions can be drawn from these results: first, that progesterone is a better substrate for prostatic 5 alpha-reductase than testosterone; second, that BPH tissue has at least two isoenzymes of 5 alpha-reductase--one in the epithelium and one (or more) in the stroma; and third, in hyperplastic prostates, most of the 5 alpha-reductase molecules are located in the stroma.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase Aged