Letrozole effect in murine ventral prostate

Abstract

The prostate gland is regulated by steroid hormones and complex interactions based on a subtle balance between androgen and estrogen (E2) regulate prostatic development and physiology. Interestingly, the changes in steroid hormone levels at old ages affect the hormonal milieu and contribute to the evolution of the pathological changes of the gland. We have analyzed the effects of letrozole, an aromatase inhibitor, on the structure in the ventral prostate of control and castrated adult rats. The results demonstrated alterations in prostate physiology after letrozole treatment. Serum levels of testosterone, prostate weight and proliferative index in luminal and basal cells were increased. Estrogen serum levels were not altered dramatically, in contrast to slight increase in gonadotrophin hormones seen in the castrated animals. Castration did not alter the proliferation index of basal cells. Reorganization of tissue compartments was seen with significant increase in letrozole treated animals. A decrease in androgen receptor expression was seen 21-days after the beginning of treatment with letrozole. These results were confirmed by immunohistochemistry. These results reveal new aspects in the relationship between androgen receptor and steroid metabolism in the prostate gland, demonstrating that alteration in hormone levels during a short time period induces significant alterations in prostate homeostasis.