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Effects of Testosterone on the Development of Muscarinic Function in the Rabbit Urinary Bladder during Puberty
Takehiro Sejima
Department of Urology, Faculty of Medicine, Tottori University, Yonago 683, Japan
The effects of testosterone (T) on muscarinic function during puberty were evaluated by measuring receptor density and contractile response to electrical field stimulation (EFS) in isolated rabbit detrusor muscle. Male New Zealand White rabbits were castrated at the age of 7 weeks (castrated group) and divided into two groups. One group was replaced by T (1.5 mg·kg-1, three times a week, subcutaneously) from the age of 9 weeks during the experimental period (T-replaced group). All animals were sacrificed at the age of 20 weeks and results were compared with those of untreated control group. Although T levels in the castrated group were continuously low, the T-replacement process brought their T Ievels nearly up to those in the control group. Castration caused a significant decrease in bladder weight Bindings of [3H]-quinuclidinyl benzilate (QNB) to the muscle membranes of three groups were saturable with dissociation constant, Kd: 0.20-0.24 nmol/L. Although there were no significant changes in Kd, the receptor density in the castrated group significantly decreased compared to that in the control group. Contractile responses of the muscle strips to EFS in the castrated group were also significantly reduced in comparison with those in the control group. In contrast, there were virtually no differences among the remaining contractilities in three groups after the atropine treatment. On the other hand, T-replacement recovered the contractility of the detrusor muscle with restoring the density of muscarinic receptors in the bladder body. These data suggest that T deficit may stunt the development of smooth muscle of the urinary bladder and reduce the cholinergic portion of contractility, probably due to the reduction in density of muscarinic receptors. Accordingly, the striking rise of circulating T Ievel may be an indispensable factor for the maturation of muscarinic function in the urinary bladder during puberty.
Key words: musclecontractility; muscarinic receptor; testosterone; puberty; urinary bladder