Effects of Surgical and Medical Androgen Deprivation on Bladder Remodeling and Steroid Receptor Expression: An...

This exploratory experimental study aimed to characterize bladder structural alterations and steroid receptor expression associated with different androgen deprivation strategies in a rat model.

Male rats were assigned to surgical castration, medical androgen deprivation with oral bicalutamide (25 mg/kg/day), leuprolide acetate (0.75 mg/kg subcutaneously on Days 1 and 14), combined androgen blockade, or control groups. Animals were evaluated after a 28-day experimental period using histopathological, morphometric, and immunohistochemical analyses. Androgen receptor (AR), estrogen receptor beta (ERβ), and caspase-3 expression were assessed to evaluate receptor-level alterations and apoptotic activity.

Androgen deprivation resulted in significant bladder remodeling characterized by urothelial alterations, smooth muscle atrophy, and a reduced smooth muscle-to-collagen ratio. These changes were most pronounced in the combined androgen blockade and surgical castration groups. AR immunoreactivity was markedly reduced in androgen-deprived groups, whereas ERβ and caspase-3 expression were significantly increased, indicating steroid receptor imbalance and enhanced apoptosis. Caspase-3 expression demonstrated a graded increase across treatment groups, with the highest levels observed in the combined androgen blockade group. Bicalutamide treatment produced intermediate changes, while leuprolide acetate showed alterations comparable to surgical castration in most parameters.

Different androgen deprivation strategies induce distinct patterns of bladder remodeling through alterations in steroid receptor expression and apoptotic pathways. These findings identify the bladder as a direct target of androgen deprivation and demonstrate a graded, receptor-mediated, and apoptosis-associated remodeling process across different ADT modalities.