Effects of castration on contraction and α1-adrenoceptor expression in rat prostate

1 The prostate function is regulated by androgens and alpha -adrenergic activity. Clinically, antiandrogens and/or alpha (1)-adrenergic antagonists are commonly used to treat symptomatic prostatic hypertrophy. To elucidate the effects of androgen deprivation on prostate contractility via alpha (1)-adrenoceptor, the characteristics and expression of alpha (1)-adrenoceptors were examined in castrated rats. 2 Isolated prostate strips from intact and castrated rats were subjected to a phenylephrine stimulated contraction. Prazosin (10 nM), [H-3]-prazosin and phenoxybenzamine (3-300 nM) were used for inhibition assay, receptor characterization and partial alkylation of alpha -adrenoceptor, respectively. The mRNA content of three subtypes of alpha -adrenoceptors was determined by reverse transcription combined with polymerase chain reaction (RT-PCR). 3 Contractile response to phenylephrine increased in castrated rats, which could be explained by a relative increase of the stromal component. A lowered contraction potency was also noted in castrated rats. Receptor binding assay indicated minimal changes in the affinity or density of alpha (1)-adrenoceptor. Escalating alkylation of the alpha (1)-adrenoceptor population resulted in a rightward shift in the contraction-response curves before depressing maximal contractile force, and the suppression was detected at lower doses in castrated rats. RT-PCR study confirmed the expression of three types of alpha (1)-adrenoceptor, alpha (1a), alpha (1b) and alpha (1d)-adrenoceptors, in intact rat prostate, and revealed that alpha (1a)-adrenoceptor, but not alpha (1b) or alpha (1d)-adrenoceptors, was down-regulated in castrates. 4 The results show that androgen deprivation suppressed alpha (1)-adrenergic contractility of rat prostate strips, and the suppression was associated with down-regulation of receptor reserve for the alpha (1a)-adreneroceptor population expressed in intact rat prostate.