Sex-related differences in the role of androgen have been reported in cardiovascular diseases and angiogenesis. Moreover, androgen receptor (AR) has been causally involved in the homeostasis of human prostate endothelial cells. However, levels of expression, functionality and biological role of AR in male- and female-derived human endothelial cells (ECs) remain poorly characterized. The objectives of this work were (1) to characterize the functional expression of AR in male- and female-derived human umbilical vein endothelial cell (HUVEC), and (2) to specifically analyze the biological effects of DHT, and the role of AR on these effects, in male-derived HUVECs (mHUVECs).

Immunohistochemical analyses of tissue microarrays from benign human tissues confirmed expression of AR in ECs from several androgen-regulated and non-androgen-regulated human organs. Functional expression of AR was validated in vitro in male- and female-derived HUVECs using quantitative RT-PCR, immunoblotting and AR-mediated transcriptional activity assays. Our results indicated that functional expression of AR in male- and female-derived HUVECs was heterogeneous, but not sex dependent. In parallel, we analyzed in depth the biological effects of DHT, and the role of AR on these effects, on proliferation, survival and tube formation capacity in mHUVECs. Our results indicated that DHT did not affect mHUVEC survival; however, DHT stimulated mHUVEC proliferation and suppressed mHUVEC tube formation capacity. While the effect of DHT on proliferation was mediated through AR, the effect of DHT on tube formation did not depend on the presence of a functional AR, but rather depended on the ability of mHUVECs to further metabolize DHT.

(1) Heterogeneous expression of AR in male- and female-derived HUVEC could define the presence of functionally different subpopulations of ECs that may be affected differentially by androgens, which could explain, at least in part, the pleiotropic effects of androgen on vascular biology, and (2) DHT, and metabolites of DHT, generally thought to represent progressively more hydrophilic products along the path to elimination, may have differential roles in modulating the biology of human ECs through AR-dependent and AR-independent mechanisms, respectively.

Forty years ago, Judah Folkman (Folkman. N Engl J Med 285: 1182-1186, 1971) proposed that tumor growth might be controlled by limiting formation of new blood vessels (angiogenesis) needed to supply a growing tumor with oxygen and nutrients. To this end, numerous "antiangiogenic" agents have been developed and tested for therapeutic efficacy in cancer patients, including prostate cancer (CaP) patients, with limited success. Despite the lack of clinical efficacy of lead anti-angiogenic therapeutics in CaP patients, recent published evidence continues to support the idea that prostate tumor vasculature provides a reasonable target for development of new therapeutics. Particularly relevant to antiangiogenic therapies targeted to the prostate is the observation that specific hormones can affect the survival and vascular function of prostate endothelial cells within normal and malignant prostate tissues. Here, we review the evidence demonstrating that both androgen(s) and vitamin D significantly impact the growth and survival of endothelial cells residing within prostate cancer and that systemic changes in circulating androgen or vitamin D drastically affect blood flow and vascularity of prostate tissue. Furthermore, recent evidence will be discussed about the expression of the receptors for both androgen and vitamin D in prostate endothelial cells that argues for direct effects of these hormone-activated receptors on the biology of endothelial cells. Based on this literature, we propose that prostate tumor vasculature represents an unexplored target for modulation of tumor growth. A better understanding of androgen and vitamin D effects on prostate endothelial cells will support development of more effective angiogenesis-targeting therapeutics for CaP patients.

The response of the prostate tissue microenvironment to androgen deprivation (AD) represents a critical component in the treatment of benign prostatic hyperplasia and prostate cancer (CaP). Primary xenografts of human benign and CaP tissue transplanted to immunocompromized SCID mice were used to characterize the response of the prostate vasculature during the initial 14 days of AD. Microvessel density and vascular lumen diameter in the prostate xenografts decreased rapidly after AD, reached a nadir on days 2-4, and recovered between days 4 and 14. The number of apoptotic endothelial cells peaked on day 2 after AD and decreased to precastration levels over days 4-7. Leakage of vascular contents in the interstitial space was apparent between days 1 and 3 after AD; however, the vascular permeability barrier reestablished between days 7 and 14. Expression of vascular endothelial growth factor (VEGF)-A, VEGF receptor-2, and basic fibroblast growth factor protein increased in endothelial cells between days 2 and 4 after AD, which preceded vascular recovery and appeared to be a direct and specific response of the endothelial cells to AD. Lack of comparable upregulation of these genes in primary cultures of human prostate endothelial cells in response to AD suggests a role for paracrine signaling mediated through stromal or epithelial cells. VEGF-A expression by prostate endothelial cells appears to represent a key facilitator of the vascular rebound in human prostate tissue induced by removal of circulating testicular androgens.

To study whether pretreatment with finasteride, compared with placebo, reduces the blood loss, operating time, amount of irrigating fluid absorbed, resources used, and other exploratory indexes of extensive surgery during transurethral resection of the prostate (TURP).

This double-blind, randomized, placebo-controlled, single-center, 6-month pilot study was designed to study the effects of 3 months of finasteride (5 mg daily) on blood loss during surgery in 60 men who required TURP. The prostate size was measured by transrectal ultrasonography, the surgical blood loss was measured by a HemoCue photometer, and fluid absorption was determined by the ethanol method. The microvessel density was counted using microscopic staining and immunoperoxidase techniques.

Finasteride significantly reduced the prostate size before TURP (P <0.001 versus placebo). No significant between-group differences were found in blood loss (geometric mean 257 and 268 mL for finasteride versus placebo), fluid absorption, operating time, resection weight, or microvessel density. A positive correlation was found between the blood loss and the resection weight. Exploratory analyses indicated that finasteride might reduce the proportion of patients with high blood loss volumes. For prostates with resection weights greater than or equal to the median (18.6 g), finasteride was associated with less blood loss (median 324 mL, n = 14) than in the controls (median 547 mL, n = 14, P <0.01).

Pretreatment with finasteride may help reduce the blood loss in TURP, except in the smallest resections.

The effects induced by oral administration of 0, 5 and 20 mg of meparticin kg(-1)of body weight for 28 days (group 1, 2 and 3, respectively) upon prostatic estrogen, androgen, alpha(1)- and beta-adrenergic receptor concentrations and on estradiol and testosterone serum levels in adult male rats were studied. The effects produced by mepartricin treatments on the weight and dimension of the gland were investigated. Both mepartricin dosages induced significant decreases (P< 0.05) of the absolute and relative weights and of the dimensions of the prostate. A significant dose-dependent decrease (P< 0.05) in estradiol serum levels was observed in treated rats, whereas no significant modifications were found in testosterone serum levels. As far as prostatic steroid receptor concentrations were concerned, a significant (P< 0.05) decrease in estrogen receptor number was observed in both treated groups, whilst a significant increase (P< 0.05) of androgen receptor concentrations was recorded only in rats treated with 20 mg mepartricin kg(-1). Conversely, a dose-dependent up-regulation of both prostatic alpha(1)- and beta-AR was found. Data obtained suggest that the prostatic alpha(1)-AR expression may be strongly influenced by estrogen deprivation (mepartricin treatment), therefore the combination of estrogen suppression (mepartricin) and adrenergic suppression (alpha(1)-AR blockers) may be suggested as a possible pharmacotherapeutic strategy for the treatment of benign prostatic hyperplasia.

We evaluated the efficacy of finasteride for the treatment of gross hematuria secondary to benign prostatic hyperplasia in a prospective fashion.

Twelve patients with recurrent episodes of gross hematuria secondary to benign prostatic hyperplasia were treated with finasteride 5 mg/day. Before initiating treatment, we excluded other sources of hematuria using intravenous urography, cystoscopy, and urine culture.

Bleeding subsided within 2 weeks of treatment in all 12 patients. Minimum follow-up was 6 months. Finasteride was well tolerated by all 12 patients.

Finasteride appears to be effective in treating recurrent gross hematuria secondary to benign prostatic hyperplasia. This therapy should be considered an alternative to transurethral resection of the prostate or hormonal ablation in patients with recurrent hematuria and no significant obstructive uropathy or adenocarcinoma of the prostate.

To review the factors that affect the concentration of prostate specific antigen (PSA) in the serum.

The discussion includes the structure of PSA; its distribution and metabolism; various analytical aspects of PSA measurements; the effects of clinical manipulations on PSA, including digital rectal examination, transrectal ultrasound, cystoscopy, biopsy and transurethral resection of the prostate; factors affecting PSA levels in health, in benign disease, and in prostate cancer; the effect of various treatments on PSA; and the issue of reference ranges.

Laboratory staff and physicians must take many factors into consideration when interpreting PSA results.