[Enzyme inhibition in the drug therapy of benign prostatic hyperplasia]

Enzyme inhibition belongs to common mechanisms of drug action and enzymes of hormone metabolism belong to targets in the treatment of benign prostatic hyperplasia. Transformation of testosterone to 5 alpha-dihydrotestosterone is catalyzed by cholestenone-5 alpha-reductase (EC 1.3.1.22, 5 alpha-reductase). Different effects of dihydrotestosterone and testosterone represent a rational basis for pharmacotherapy by 5 alpha-reductase inhibition. The enzyme is active in the prostate and other organs and tissues, with different distribution of at least two 5 alpha-reductase isoenzymes. Beside this, progesterone-5 alpha-reductase (EC 1.3.1.30) as another enzyme with 5 alpha-reductase activity is present in human tissues including the prostate. The existence of several 5 alpha-reductase activities gives bright possibilities of 5 alpha-reductase inhibition. Basic 5 alpha-reductase inhibitors are synthetic steroid (e.g. finasteride--Proscar). Various mechanisms of their effect (classical reversible competitive inhibition, mechanism-based "suicide" inhibitors, tightly bound irreversible inhibitors...) represent different pharmacokinetic patterns, too. Non-steroidal 5 alpha-reductase inhibitors (e.g. polyunsaturated fatty acids) are effective components of several phytopharmaceuticals. They receive attention due to their complexity and low hazards. Extracts of Serenoa repens seeds (Permixon, Capistan in the Czech Republic), of Pygeum africanum, of Urtica radicis roots (Urtica, Urtiron) or catequine structures from the green tea belong to this group. Beside androgens, participation of estrogens in the origin and development of benign prostatic hyperplasia is probable. Inhibition of the "aromatase" complex, which catalyzes transformation of androgens to estrogens, may contribute to the complexity of phytotherapeutic effects.