Evidence for activation of the renin-angiotensin system in the human prostate: increased angiotensin II and reduced AT(1) receptor expression in benign prostatic hyperplasia.
The expression and cellular localization of angiotensin II (Ang II) and AT(1) receptor proteins were examined in the normal human prostate and benign prostatic hyperplasia (BPH) by immunohistochemistry. In the normal prostate, Ang II immunoreactivity was localized to the basal layer of the epithelium and AT(1) receptor immunostaining was found predominantly on stromal smooth muscle and also on vascular smooth muscle of prostatic blood vessels. Ang II immunoreactivity was markedly increased in hyperplastic acini in BPH compared with acini in the normal prostate (normal: 7.4+/-0.2%, n=5 vs. BPH: 22.7+/-1.9%, n=5, p<0.001). However, AT(1) receptor immunoreactivity was significantly decreased in BPH compared with the normal prostate [normal: 16.4+/-2.2%, n=4 vs. BPH: 9.4+/-1.3%, n=5, p<0.05 (p=0.025)]. The present study demonstrates the presence of Ang II peptide in the basal layer of the epithelium and AT(1) receptors on stromal smooth muscle, suggesting that Ang II may mediate paracrine functions on cellular growth and smooth muscle tone in the human prostate. Furthermore, AT(1) receptor down-regulation in BPH may be due to receptor hyperstimulation by increased local levels of Ang II in BPH. These data extend previous findings in support of the novel concept that overactivity of the renin-angiotensin system (RAS) may be involved in the pathophysiology of BPH.
Dinh
Diem T
DT
Department of Medicine, University of Melbourne, Austin & Repatriation Medical Centre, Heidelberg, VIC 3084, Australia.
Frauman
Albert G
AG
Somers
Gino R
GR
Ohishi
Mitsuru
M
Zhou
Jialong
J
Casley
David J
DJ
Johnston
Colin I
CI
Fabiani
Maurice E
ME
D000803:Angiotensin I / Q000378:metabolism*; D000804:Angiotensin II / Q000032:analysis*; D016022:Case-Control Studies; D004848:Epithelium / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000737:chemistry; D011467:Prostate / Q000098:blood supply / Q000737:chemistry*; D011470:Prostatic Hyperplasia / Q000378:metabolism*; D011945:Receptors, Angiotensin / Q000032:analysis*; D012084:Renin-Angiotensin System / Q000502:physiology*
D011945:Receptors, Angiotensin; D000804:Angiotensin II; D000803:Angiotensin I