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  • Title: Effects of castration on contraction and alpha(1)-adrenoceptor expression in rat prostate.
    Author: Homma Y, Hamada K, Nakayama Y, Tsujimoto G, Kawabe K.
    Journal: Br J Pharmacol; 2000 Dec; 131(7):1454-60. PubMed ID: 11090120.
    Abstract:
    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), [(3)H]-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.
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