Progesterone reduces epithelial proliferation and attenuates prostatic hyperplasia in Spontaneously Hypertensive Rats

Considering little is known about the effects of progesterone (P4) on prostate biology, this study aimed to evaluate the influence of P4 on the ventral prostate of spontaneously hypertensive rats (SHR). 30-week-old male SHR were subjected to hormone or vehicle administration. P4 was administered at a dose of 70mg/kg/day (SHP and SHPT groups) and testosterone cypionate (T) at 1mg/kg/day (SHT and SHPT groups) for 4 weeks. Control groups (SHC, SHCT, and SHCC) received the corresponding volume of the vehicle following the same protocol. At the end of treatment (8.5 months of age), ventral prostates were collected and subjected to biometrical, morphological, morphometrical, stereological, biochemical, ultrastructural, histopathological, serological, and immunohistochemical analyses. P4 promoted a reduction in both total and relative weights of all prostatic lobes, even when administered in combination with T. However, only SHP animals showed a reduced relative frequency of alveoli exhibiting intense hyperplasia. In addition, a marked reduction in epithelial cell proliferation was observed in animals treated with P4 alone or associated with T. Collectively, these findings demonstrate that P4 induces a pronounced reduction in prostate size, attenuates prostatic hyperplasia in SHR, and exerts a potent antiproliferative effect on epithelial cells of the ventral prostate. These effects may result from tissue atrophy induced by the systemic effects of P4. However, a direct action of P4, mediated through genomic and/or non-genomic mechanisms, either independently or in combination with its systemic effects, cannot be ruled out.