Effect of neonatal estrogenization on testosterone metabolism in the prostate and in the epididymis of the rat.

The present experiments were performed in order to analyze whether the administration of estrogens (single injection of 500 micrograms of estradiol benzoate s.c.) to neonatal male rats might modify the weight of the ventral prostate and the epididymis as well as the metabolism of testosterone in these two organs.

Antihormonal activities of 5 alpha-reductase and aromatase inhibitors.

The problem of developing androgen antagonists has been tackled so far only by synthesizing steroids able to displace testosterone and other androgens from their specific receptor sites. The observation that testosterone has to be converted intracellularly either to 5 alpha-reduced metabolites (DHT, 3 alpha-diol, etc.) or to estrogens, in order to become fully active on androgen-dependent structures (both central and peripheral), has opened the possibility of creating molecules which prevent these conversions, and which could then block the actions of testosterone.

New approaches for the treatment of prostatic hypertrophy and cancer.

The present study reports the effects exerted by 4-hydroxy-4-androstene-3,17-dione (4-OH-A) on the in vitro metabolism of labelled testosterone, dihydrotestosterone (DHT) and androstenedione (delta-4-A) in the prostate of adult male rats and in human benign prostatic hypertrophic (BPH) tissue. It has been found that 4-OH-A decreases the formation of DHT and of the diols. When testosterone is used as the substrate, the presence in the medium of 4-OH-A enhances the formation of delta-4-A and of 5-alpha-androstanedione (5-alpha-A); 4-OH-A does not inhibit the conversion of labelled DHT into the diols.

In vitro effects of an aromatase inhibitor on 5 alpha-reductase activity in human hypertrophic prostatic tissue.

To determine the effects of 4-hydroxy-4-androstene-3,17-dione (4-OH-A) on the in vitro conversion of testosterone (T) to 5 alpha-androstan-17 beta-ol-3-one (dihydrotestosterone, DHT), 5 alpha-androstan-3 alpha, 17 beta-diol and 5 alpha-androstan-3 beta, 17 beta-diol (diols), human benign hypertrophic prostatic (BPH) tissue was incubated with 4-14C-T as substrate, in the presence of 4-OH-A (10(-8) to 10(-6) M); the amounts of the 5 alpha-reduced metabolites formed were quantitated. The effects of 4-OH-A were compared with those of 17 beta-N,N-diethylcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one (4-MA), a known inhibitor of the 5 alpha-reductase. In the absence of 4-OH-A and 4-MA, human BPH tissue converted T to DHT and the diols readily.