Effects of castration on contraction and α 1 ‐adrenoceptor expression in rat prostate

The prostate function is regulated by androgens and α‐adrenergic activity. Clinically, antiandrogens and/or α 1 ‐adrenergic antagonists are commonly used to treat symptomatic prostatic hypertrophy. To elucidate the effects of androgen deprivation on prostate contractility via α 1 ‐adrenoceptor, the characteristics and expression of α 1 ‐adrenoceptors were examined in castrated rats. Isolated prostate strips from intact and castrated rats were subjected to a phenylephrine stimulated contraction. Prazosin (10 n M ), [ 3 H]‐prazosin and phenoxybenzamine (3–300 n M ) were used for inhibition assay, receptor characterization and partial alkylation of α‐adrenoceptor, respectively. The mRNA content of three subtypes of α‐adrenoceptors was determined by reverse transcription combined with polymerase chain reaction (RT–PCR). 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 α 1 ‐adrenoceptor. Escalating alkylation of the α 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 α 1 ‐adrenoceptor, α 1a , α 1b and α 1d ‐adrenoceptors, in intact rat prostate, and revealed that α 1a ‐adrenoceptor, but not α 1b or α 1d ‐adrenoceptors, was down‐regulated in castrates. The results show that androgen deprivation suppressed α 1 ‐adrenergic contractility of rat prostate strips, and the suppression was associated with down‐regulation of receptor reserve for the α 1a ‐adreneroceptor population expressed in intact rat prostate.British Journal of Pharmacology (2000) 131 , 1454–1460; doi: 10.1038/sj.bjp.0703706