Inhibition of Enzymes in the Pharmacological Treatment in of Benign Prostatic Hyperplasia

Overview

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

Key words:
pharmacotherapy, benign prostatic hyperplasia, 5α-reductase, aromatase, enzyme inhibitors, phytopharmaceuticals.