Nerve-evoked and phasic contractions of the rat bladder: Effects of low testosterone and treatment with the selective and rogen receptor modulator trenbolone

Overactive bladder is prevalent with aging and recent evidence suggests androgen deficiency may playa role (Koritsiadis et al., 2008). Androgen receptors are expressed throughout the bladder (Chalvamane et al., 2010),although the role of testosterone in bladder function remains unclear.Aims. To investigate the effect of low testosterone and treatment with a selective androgen receptor modulator oncontractility of rat bladder strips.Methods. Wistar rats (8 weeks) were orchiectomised (5% isoflurane). 8 weeks later, half received trenboloneacetate (2mg/kg/day for 8 weeks, sc.). Sham-operated controls received vehicle. Isolated bladder strips weremounted in tissue baths (Krebs-bicarbonate solution, 1.5g tension, 37°C). Amplitude and frequency of phasiccontractions (PCs) and nerve-evoked contractions (EFS) (1-50Hz, 0.01ms duration, 40V, 5s every 100s) wereexamined.Results. Orchiectomised rats had low serum testosterone vs controls and trenbolone-treated (0.24±0.05 vs 1.68±0.18vs 0.21±0.04ng/ml, P<0.001). Amplitude of PCs was increased in orchiectomised rat bladder strips (0.0266±0.0025vs 0.0016±0.0027g/mg, P<0.05), whilst frequency was reduced (32±5 vs 50±5 events/5mins, P<0.05). Trenbolonetreatmentprevented the increased amplitude, but not the decreased frequency. EFS contractions were depressed inorchiectomised bladder strips and α,β-methylene-ATP (10μM) produced greater inhibition vs controls (80.3±2.8%vs 6.6±3.8%, P<0.01). Trenbolone-treatment did not prevent depressed EFS contractions, but did prevent theincreased purinergic component. Atropine (1μM) plus α,β-methylene-ATP completely abolished EFS responses inorchiectomised bladder strips, but not in control and trenbolone-treated, where the remaining response wasunaffected by L-NNA (100μM).Discussion. Orchiectomy causes increased phasic contractions of rat bladder strips and depressed nerve-evokedcontractions, in which ATP plays a greater role, supporting a role for testosterone in normal bladder function.Trenbolone prevented only some of these alterations, suggesting the actions of testosterone may be partly mediatedvia conversion to other sex steroids.