Effects of androgen deprivation on prostate alpha 1-adrenergic receptors.
OBJECTIVE
Benign prostatic hyperplasia (BPH), the most common benign tumor in men, consists of two components-static (enlargement regulated 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 androgen deprivation and replacement on regulation of rat ventral prostate alpha 1-ARs.


METHODS
Prostate weight, alpha 1-AR density, autoradiographic images, histologic features, and cell-specific protein were examined before and after castration and androgen replacement.


RESULTS
Castration decreases ventral prostate wet weight, a process reversed by testosterone administration. In contrast, there is an apparent increase in alpha 1-AR density (29 +/- 4 versus 65 +/- 6 fmol/mg total protein, mean +/- SEM) after castration, returning to baseline with testosterone replacement; alpha 1-AR density remains constant in control liver membranes. Alpha 1-ARs predominate in stroma throughout androgen deprivation therapy. Epithelially derived cells decrease (83% to 67%) after castration, resulting in a relative doubling in stroma (17% to 33%); the protein content of epithelial and stromal cells remains identical. Therefore, prostate-specific increases in alpha 1-ARs appear to result from relative increases in the ratio of smooth muscle to epithelium after castration rather than from direct upregulation of alpha 1-AR protein.


CONCLUSIONS
Because alpha 1-AR density does not decrease with androgen deprivation, these studies suggest that alpha 1-AR antagonists remain an important component in BPH therapy, even when 5-alpha-reductase inhibitors are utilized.
Lacey
J P
JP
Department of Surgery (Urology), Duke University Medical Center, Durham, North Carolina 27710, USA.
Donatucci
C F
CF
Price
D T
DT
Page
S O
SO
Bennett
S A
SA
Tenniswood
M P
MP
Schwinn
D A
DA
D000818:Animals; D001345:Autoradiography; D008297:Male; D009919:Orchiectomy; D009929:Organ Size; D011470:Prostatic Hyperplasia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D011506:Proteins / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000032:analysis / Q000502:physiology*
D011506:Proteins; D018340:Receptors, Adrenergic, alpha-1