Endocrine Abstracts

Prostate and seminal vesicles are male accessory sex glands secreting fluids that, together with sperm, form the semen. Clear evidence indicating these organs depend on androgens was found the men suffering hypogonadism because, in them, the function of these glands decreases markedly. Because prostate and seminal vesicles are androgen-dependent organs, they have been used as a model to test antiandrogenic drugs in different animal species.

The objective of this study was to demonstrate the antiandrogenic effect of two pure, novel, and non-steroidal molecules (JP01B and JP03) on the hamster’s prostate and seminal vesicles.

The biological activity of both compounds was determined as in vivo as in vitro experiments. The in vivo experiments were performed in hamsters castrated and treated with testosterone (T), T, and finasteride/or each one of the new compounds. For the in vitro experiments to determine the metabolism of radiolabeled T en the presence or absence of JP01B and JP03, we followed the conversion of T into their radiolabeled metabolites using the human prostate homogenates as a source of steroidal enzymes. The results indicated that JP01B and JP03 significantly decreased the weight of the seminal vesicles but not that of the prostate. However, treatment with T and finasteride (an inhibitor of DHT formation) reduced the mass of both glands. In vitro experiments indicated that both new compounds inhibited the activity of the AK1C enzyme by decreasing the formation of labeled 5α-androstane-3β, 17β-diol compared to the control. However, an accumulation of 5α-dihydrotestosterone (DHT) was determined, which also indicates the presence of the enzyme 5α-reductase. It is a well-known fact that DHT increases the weight of the prostate and seminal vesicles. These data could explain that hamsters treated with T and JP01B or T and JP03 did not reduce prostate growth. However, this does not clarify why the seminal vesicles did significantly reduce their weight. One interpretation could be the presence of estrogen receptor β (ERβ) in this tissue, as has been previously demonstrated. The ERβ is capable of inducing mitosis of epithelial cells, cell morphogenesis, and secretory modulation of specific proteins in the seminal vesicles. Therefore, data suggest that JP01B and JP03 could also be ERβ antagonists in seminal vesicles.