EFFECTS OF ANDROGEN DEPRIVATION ON PROSTATE ALPHA(1)-ADRENERGIC RECEPTORS

Objectives. Benign prostatic hyperplasia (BPH), the most common benign tumor in men, consists of two components-static (enlargement regulate d by androgens) and dynamic (smooth muscle contraction through alpha(1 )-adrenergic receptors [alpha(1)-ARs]). Because medical therapy of BPH involves tissue androgen deprivation, we studied the influence of and rogen deprivation and replacement on regulation of rat ventral prostat e alpha(1)-ARs. Methods. Prostate weight, alpha(1)-AR density, autorad iographic images, histologic features, and cell-specific protein were examined before and; after castration and androgen replacement. Result s, Castration decreases ventral prostate wet weight, a process reverse d by testosterone administration. In contrast, there is an apparent in crease in alpha(1)-AR density (29 +/- 4 versus 65 +/- 6 fmol/mg total protein, mean +/- SEM) after castration, returning to baseline with te stosterone replacement; alpha(1)-AR density remains constant in contro l liver membranes, Alpha(1)-ARs predominate in stroma throughout andro gen deprivation therapy. Epithelially derived cells derived (83% to 67 %) after castration, resulting in a relative doubling in stroma (17% t o 35%): the protein content of epithelial and stromal cells remains id entical. Therefore, prostate-specific increases in alpha(1)-ARs appear to result from relative increases in the ratio of smooth muscle to ep ithelium after castration rather than from direct upregulation of alph a(1)-AR protein. Conclusions, Because alpha(1)-AR density does not dec rease with androgen deprivation, these studies suggest that alpha(1)-A R antagonists remain an important component in BPH therapy, even when 5-alpha-reductase inhibitors are utilized.