|
121. The monkey and human uridine
diphosphate-glucuronosyltransferase UGT1A9, expressed in
steroid target tissues, are estrogen-conjugating
enzymes.
Albert C, Vallee M, Beaudry G, Belanger A, Hum DW
Laboratory of Molecular Endocrinology, CHUL Research Center,
Laval University, Quebec, Canada.
[Medline record in process]
Endocrinology 1999 Jul;140(7):3292-302
Considering the physiologic importance of the steroid
response, which is regulated in part by steroid levels in a
given tissue, relatively little is known about steroid
glucuronidation, which is widely accepted as a major pathway
involved in the catabolism and elimination of steroid hormones
from the human body. In a previous study, it was ascertained
that the monkey may be the most appropriate model in which to
examine the role of steroid glucuronidation. Northern blot
analysis of simian RNA, hybridized with human UGT
complementary DNA (cDNA) probes demonstrate the similarity of
the transcripts. The simian UGT1A09 cDNA isolated from a liver
library is 2396 bp and contains an open reading frame encoding
530 amino acids. The predicted primary structure is most
homologous to the human UGT1A9 (hUGT1A9) enzyme, which share
93% identity. Stable transfection of the monkey UGT1A09
(monUGT1A09) cDNA into HK293 cells, expresses a microsomal
protein with an apparent molecular mass of 55 kDa. Of the more
than 30 endogenous substrates tested, both proteins show the
highest activity on 4-hydroxyestradiol and 4-hydroxyestrone,
followed by 2-hydroxyestradiol and estradiol. RT-PCR analysis
demonstrate that UGT1A9 transcript is expressed in several
tissues, which include the prostate, testis, breast, ovary,
and skin of the monkey and humans. The expression of UGT1A9 in
extrahepatic estrogen-responsive tissues, and its high
activity on estrogens is consistent with this enzyme having a
role in estrogen metabolism.
122. Imprinting by Neonatal Sex Steroids on the
Structure and Function of the Mature Mouse Prostate.
Singh J, Handelsman DJ
Department of Medicine, DO2, University of Sydney, Sydney,
New South Wales 2006, Australia.
[Record supplied by publisher]
Biol Reprod 1999 Jul;61(1):200-208
Perinatal sex-steroid exposure may result in permanent
modifications in the structure and function of the prostate
gland. The mechanism of such long-range alterations in
hormonal sensitivity is not known. This study aimed to define
the molecular requirements for neonatal sex-steroid imprinting
and to investigate whether combined administration of neonatal
androgens and estrogens had synergistic effects upon the
mature mouse prostate. Since the interaction between
endogenous and exogenous sex steroids in normal mice makes it
difficult to dissociate direct from indirect effects, we used
the hypogonadal (hpg) mouse, characterized by congenital
androgen deficiency yet still fully responsive to exogenous
androgens. Newborn mice (Days 1-2) were administered a single
s.c. injection of androgens alone or in combination with an
estrogen followed by testosterone-induced maximal prostate
growth at maturity. The final effects were determined in
7-wk-old mice through study of ductal architecture in
microdissected ventral prostates (VP) and quantitation of
volume densities and diameters of prostate tissue components.
A single neonatal dose of androgens, but not of estrogen,
increased branching morphogenesis and VP weights at adulthood.
These effects did not differ significantly between various
androgens; in addition, combined androgen and estrogen
treatment failed to demonstrate any synergistic effects on the
prostate. We conclude that neonatal androgens induce
long-range effects upon the mature VP structure as well as its
secretory function and that this imprinting occurs via the
androgen receptor without requiring aromatization of
androgens. However, these conclusions, based on a specific
treatment protocol, are confined only to the distal segment of
VP, and effects of neonatal sex-steroid exposure in other
regions
123. Mitogen-activated protein kinase kinase kinase
1 activates androgen receptor-dependent transcription and
apoptosis in prostate cancer.
Abreu-Martin MT, Chari A, Palladino AA, Craft NA, Sawyers
CL
Department of Medicine, Cedars-Sinai Medical Center, Los
Angeles, California 90095, USA.
Mol Cell Biol 1999 Jul;19(7):5143-54
Mitogen-activated protein (MAP) kinases phosphorylate the
estrogen receptor and activate transcription from estrogen
receptor-regulated genes. Here we examine potential
interactions between the MAP kinase cascade and androgen
receptor-mediated gene regulation. Specifically, we have
studied the biological effects of mitogen-activated protein
kinase kinase kinase 1 (MEKK1) expression in prostate cancer
cells. Our findings demonstrate that expression of
constitutively active MEKK1 induces apoptosis in androgen
receptor-positive but not in androgen receptor-negative
prostate cancer cells. Reconstitution of the androgen receptor
signaling pathway in androgen receptor-negative prostate
cancer cells restores MEKK1-induced apoptosis. MEKK1 also
stimulates the transcriptional activity of the androgen
receptor in the presence or absence of ligand, whereas a
dominant negative mutant of MEKK1 impairs activation of the
androgen receptor by androgen. These studies demonstrate an
unanticipated link between MEKK1 and hormone receptor
signaling and have implications for the molecular basis of
hormone-independent prostate cancer growth.
124. Neonatal estrogen exposure alters the
transforming growth factor-beta signaling system in the
developing rat prostate and blocks the transient
p21(cip1/waf1) expression associated with epithelial
differentiation.
Chang WY, Birch L, Woodham C, Gold LI, Prins GS
Department of Urology, University of Illinois College of
Medicine, Chicago 60612, USA.
Endocrinology 1999 Jun;140(6):2801-13
Exposure of male rats to estrogens during the neonatal
period retards prostate branching morphogenesis, blocks
epithelial differentiation, and predisposes the adult prostate
to hyperplasia and dysplasia. The mechanism of neonatal
estrogenization is not well understood. The present study
evaluated transforming growth factor-beta (TGFbeta) in the
neonatally estrogenized ventral prostate to determine whether
this paracrine/autocrine factor may in part mediate the
effects ofestrogen on the developing prostate gland.
Immunocytochemistry using antibodies against active TGFbeta1
and its latency-associated peptide localized this molecule to
the periductal smooth muscle cells in the developing prostate.
Although neonatal estrogenization increased the accumulation
of total and active TGFbeta1 in the smooth muscle layer as
early as day 6 of life, it was physically separated from the
epithelial ducts by a proliferating layer of fibroblasts
surrounding the basement membrane. RT-PCR demonstrated that
alterations in TGFbeta1 levels were not due to alterations in
TGFbeta1 transcription. TGFbeta2 and TGFbeta3 were primarily
immunolocalized to differentiating epithelial cells in
developing prostates, and this was markedly dampened between
days 10-30 after neonatal estrogen exposure.
Immunocytochemistry for TGFbeta signaling components revealed
that neonatal estrogenization transiently reduced TGFbeta type
I receptor levels in the prostate epithelium, but not in
stroma, between days 6-15, whereas there was no effect on
TGFbeta type II receptor. Levels of the intracellular signal
Smad2 (52 kDa) were detected in epithelial cells but were not
altered after estrogenization. To analyze the functional
status of the TGFbeta signaling pathway, immunocytochemistry
was performed for p21(cip-1/waf-1), a cyclin-dependent kinase
inhibitor that is inducible by TGFbeta1 in the prostate.
Transient nuclear localization of p21(cip-1/waf-1) was
normally observed in epithelial cells between days 6-15 and
was associated with entry of cells into a terminal
differentiation pathway. Neonatal estrogenization prevented
this transient expression of p21(cip-1/waf-1). The present
findings demonstrate that the TGFbeta signaling system is
perturbed at several levels in the estrogenized prostate,
which may in part account for the epithelial cell
differentiation blockade as well as the proliferation of
periductal fibroblasts in this model.
125. Expression of pepsinogen II with androgen and
estrogen receptors in human prostate carcinoma.
Konishi N, Nakaoka S, Matsumoto K, Nakamura M, Kuwashima S,
Hiasa Y, Cho M, Uemura H, Hirao Y
Second Department of Pathology, Nara Medical University,
Kashihara, Japan.
nkonishi@naramed-u.ac.jp
Pathol Int 1999 Mar;49(3):203-7
The expression of pepsinogen II (PG II), an aspartyl
proteinase usually involved in the digestion of proteins in
the stomach, was immunohistochemically investigated in
conjunction with androgen (AR) and estrogen receptor (ER)
status in prostate adenocarcinomas. Of a total of 38 samples
obtained from radical prostatectomies, 23 tumors (60.5%) were
positive for PG II and there was a significant positive
correlation to the expression of AR but not to ER. Cells
positive for PG II were localized mainly to the peripheral
zones of tumorous glands which, in normal prostate, are
negative, and in areas also expressing AR. In addition, a
significant correlation between AR and ER was detected in the
prostate carcinomas examined, which suggests a
hormone-dependent status. On the basis of these results, PG II
expression might be closely related to hormonal alterations
associated with the development of prostate tumors
126. Phosphorylation/dephosphorylation of androgen
receptor as a determinant of androgen agonistic or
antagonistic activity.
Wang LG, Liu XM, Kreis W, Budman DR
Department of Medicine, New York University School of
Medicine, North Shore University Hospital, Manhasset, New
York, 11030, USA.
Biochem Biophys Res Commun 1999 May
27;259(1):21-8
Protein phosphorylation/dephosphorylation is an important
posttranslational modification that plays a critical role in
signal transduction. The androgen receptor (AR) is under such
control. We demonstrate that androgen receptor phosphorylation
determines whether or not AR ligands perform as agonists or
antagonists in LNCaP cells. Androgen receptor ligands (such as
dihydrotestosterone and beta-estradiol) stimulate receptor
expression and phosphorylation and, as a result, they act as
agonists or partial agonists. In contrast, agents such as
bicalutamide and estramustine inhibit the receptor
phosphorylation and act as antagonists. This model is
supported by gene expression and transactivation assays.
Significant increases in levels of both mRNA and protein of
prostate-specific antigen (PSA), a natural AR target gene,
occur following the treatment of LNCaP cells with DHT,
beta-estradiol, or hydroxyflutamide. In contrast, exposure of
LNCaP cells to bicalutamide or estramustine results in a sharp
decrease of PSA expression. Agonistic or antagonistic effect
of these compounds on PSA expression parallels the level of
phosphorylated, but not dephosphorylated androgen receptors.
These agonistic or antagonistic effects are also observed in
HeLa cells transfected with wild-type AR expression plasmid
(pAR0) and AR-driven luciferase expression plasmid GRE-tk-LUC
in the presence of different groups of AR blockers. Our data
indicate that the functional status of androgen receptors is
strongly correlated with the phosphorylation status of the
receptors, and that the phosphorylated androgen receptor is
the form of the receptor transcriptionally active in
regulation. Thus the androgen receptor
phosphorylation/dephosphorylation
127. The estrogen receptor beta subtype: a novel
mediator of estrogen action in neuroendocrine systems.
Kuiper GG, Shughrue PJ, Merchenthaler I, Gustafsson JA
Department of Medical Nutrition, Karolinska Institute, Novum,
Huddinge, S-14157, Sweden.
george.kuiper@cbt.ki.se
Front Neuroendocrinol 1998 Oct;19(4):253-86
The recent discovery that an additional estrogen receptor
(ERbeta) subtype is present in many rat, mouse, and human
tissues has advanced our understanding of the mechanisms
underlying estrogen signalling. Ligand-binding experiments
have shown specific binding of 17beta-estradiol by ERbeta with
an affinity similar to that of ERalpha. The rat tissue
distribution and/or the relative level of ERalpha and ERbeta
expression seems to be quite different, i.e., moderate to high
expression in uterus, testis, pituitary, ovary, kidney,
epididymis, and adrenal for ERalpha and prostate, ovary, lung,
bladder, brain, bone, uterus, and testis for ERbeta. Within
the same organ it often appears that the ER subtypes are
expressed in different cell types, supporting the hypothesis
that the ER's may have different biological functions. The
cell type-specific expression of ERalpha and ERbeta in rat
prostate, testis, uterus, ovary, and brain and the
distribution of ERbeta mRNA in the ERalpha knock-out mouse
brain are discussed. The discovery of ERbeta suggests the
existence of two previously unrecognized pathways of estrogen
signalling; via the ERbeta subtype in tissues exclusively
expressing this subtype and via the formation of heterodimers
in tissues expressing both ER subtypes. The existence of two
ER subtypes, their differential expression pattern, and
different actions on certain response elements could provide
explanations for the striking species-, cell-, and
promoter-specific actions of estrogens and antiestrogens. The
challenge for the future is to unravel the detailed
physiological role of each subtype and to use this knowledge
to develop the next generation of ER-targeted drugs with
improved therapeutic profiles in the treatment or prevention
of osteoporosis, cardiovascular system disorders, Alzheimer's
disease, breast cancer, and disorders of the urogenital
tract.
128. The novel estrogen receptor-beta subtype:
potential role in the cell- and promoter-specific actions of
estrogens and anti-estrogens.
Kuiper GG, Gustafsson JA
Center for Biotechnology and Department of Medical Nutrition,
Karolinska Institute, NOVUM, Huddinge, Sweden.
george.kuiper@cbt.ki.se
FEBS Lett 1997 Jun 23;410(1):87-90
The recent discovery that an additional estrogen receptor
(ER) subtype is present in various rat, mouse and human
tissues has advanced our understanding of the mechanisms
underlying estrogen signalling. The discovery of a second ER
subtype (ERbeta) suggests the existence of two previously
unrecognised pathways of estrogen signalling: via the ERbeta
subtype in tissues exclusively expressing this subtype and via
the formation of heterodimers in tissues expressing both ER
subtypes. Various models have been suggested as explanations
for the striking cell- and promoter-specific effects of
estrogens and anti-estrogens, all on the basis of the
assumption that only a single ER gene
129. Identification of a splice variant of the rat
estrogen receptor beta gene.
Chu S, Fuller PJ
Prince Henry's Institute of Medical Research, Clayton,
Victoria, Australia.
Mol Cell Endocrinol 1997 Sep 19;132(1-2):195-9
Recently a second estrogen receptor termed estrogen
receptor beta (ERbeta) has been cloned and characterized, and
shown to be expressed at the highest levels in ovarian
granulosa cells and prostatic epithelium. In the course of
amplifying a region of the ligand-binding domain of the rat
ERbeta cDNA we identified a second, larger transcript which
appears to arise through differential splicing. The second
isoform has 54 nucleotides inserted after position 1372
encoding 18 additional amino acids. Both isoforms are
expressed at similar relative abundance in a range of
tissues.
130. Therapeutic potential of selective estrogen
receptor modulators.
Gustafsson JA
Department of Medical Nutrition, Karolinska Institute, Novum,
Huddinge, Sweden.
Curr Opin Chem Biol 1998 Aug;2(4):508-11
The hormone estradiol has effects on many tissues in both
males and females. Some of these effects, such as inhibition
of cancer growth and modulation of the devastating effects of
aging on bone, brain, skin and bladder, are good. Others, such
as the effect on the breast and endometrium, are undesirable.
The task of designing drugs that would have only the good
effects of estradiol has, until recently, seemed almost
impossible because it was thought that there was only one
estrogen receptor and that an estrogenic agent was
definitively categorized as an estrogen agonist or an
antagonist. More recently we have learnt that there are two
estrogen receptors which, under certain conditions, have
opposite effects on gene transcription. In addition, it is now
understood that agents cannot be described as agonists or
antagonists because a single agent can be an agonist in one
tissue and an antagonist in another. The term 'selective'
estrogen receptor modulator' was designed to incorporate this.
The idea of estrogen receptor modulators has raised new hope
that tissue specific estrogens or anti-estrogens can be
designed.
131. Estrogen receptor in human benign prostatic
hyperplasia.
Donnelly BJ, Lakey WH, McBlain WA
J Urol 1983 Jul;130(1):183-7
Estrogens have been proposed as a major etiological factor
in the pathogenesis of benign prostatic hyperplasia in man.
The presence of estrogen receptor in benign prostatic
hyperplasia would support this concept. Using the receptor
stabilizer, sodium molybdate, and a hydroxylapatite assay we
assayed human benign prostatic hyperplasia for the presence of
cytosolic estrogen receptor. For comparison, we assayed
estrogen receptor in cytosols of prostatic cancer and normal
tissue, and we also measured androgen receptor and
progesterone receptor concentrations in the 3 tissue types.
Estrogen receptor was present in 8 of 15 benign prostatic
hyperplasia specimens at a mean concentration of 9.2 fmol./mg.
protein for the estrogen-receptor-positive samples. Sucrose
gradient analysis of the estrogen receptor of benign prostatic
hyperplasia revealed that it sedimented in the region of 8S,
and steroid specificity studies confirmed that the binding to
estrogen receptor was estrogen-specific. Estrogen receptor was
also found in normal (3 of 3) and malignant (4 of 6) tissues,
and all tissues were positive for androgen receptor. The
presence of estrogen receptor in human benign prostatic
hyperplasia supports the proposal that circulating estrogens
may have a role in the pathogenesis of this disorder.
132. Estrogen receptors in human prostate: evidence
for multiple binding sites.
Ekman P, Barrack ER, Greene GL, Jensen EV, Walsh PC
J Clin Endocrinol Metab 1983 Jul;57(1):166-76
The existence of estrogen receptors in the human prostate
has long been a controversial issue. This may be explained
partly by the apparent heterogeneity of estrogen-binding sites
in prostatic tissue. We herein report on multiple binding
sites for estrogens in cytosol as well as nuclear preparations
of human prostatic tissues. One class of binding sites
corresponds to the classical, high affinity estrogen receptor;
the Kd for [3H]estradiol binding to the receptor was
approximately 0.10 nM and the binding was specific for
estrogens. The second class of binding sites appeared to have
a Kd for [3H]estradiol in the range of 5-10 nM. This second,
lower affinity class of binding sites markedly influenced
studies of the classical receptor even at low ligand
concentrations. Saturation analysis should be performed over a
wide range of ligand concentrations (0.05-10 nM) to allow
separation of the two binding components. Quantitation of
estrogen receptor by a single point assay cannot be carried
out accurately unless the low affinity binding component can
be blocked. Multiple binding sites for estradiol were observed
in the cytosol as well as in the nuclear salt extractable and
salt-resistant compartments of normal, benign hyperplastic,
and cancerous human prostates. Normal peripheral and cancerous
prostates contained significantly (P less than 0.01) higher
amounts of cytosol estrogen receptor compared to benign
hyperplastic tissue.
133. Steroid hormone receptors in prostatic
hyperplasia and prostatic carcinoma.
Khalid BA, Nurshireen A, Rashidah M, Zainal BY, Roslan BA,
Mahamooth Z
Department of Medicine, Universiti Kebangsaan Malaysia, Kuala
Lumpur.
Med J Malaya 1990 Jun;45(2):148-53
One hundred and six prostatic tissue samples obtained from
transurethral resection were analysed for androgen and
estrogen receptors. In 62 of these, progesterone and
glucocorticoid receptors were also assayed. Steroid receptors
were assayed using single saturation dose 3H-labelled ligand
assays. Ninety percent of the 97 prostatic hyperplasia tissues
and six of the nine prostatic carcinoma tissues were positive
for androgen receptors. Estrogen receptors were only present
in 19% and 33% respectively. Progesterone receptors were
present in 70% of the tissues, but glucocorticoid receptors
were present in only 16% of prostatic hyperplasia and none in
prostatic carcinoma.
134. Estrogen receptors and clinical correlations
with human prostatic disease.
Pontes JE, Karr JP, Kirdani RY, Murphy GP, Sandberg AA
Urology 1982 Apr;19(4):399-403
Measurement of estrogen binding in human prostate using
high-pressure liquid chromatography (HPLC) revealed the
presence of cytosolic estrogen receptors (ER) both in benign
prostatic hyperplasia (BPH) and adenocarcinoma. Receptor
concentrations correlated with several histopathologic
features in the specimens analyzed. Estrogen receptor levels
generally were higher in BPH than in cancer specimens although
there was a subgroup of patients with poorly differentiated
carcinoma with levels higher than those of BPH, HPLC can be
used for measuring ER in 50 microliters of cytosol, and thus
needle biopsy specimens will be analyzed routinely for ER with
this micromethod.
135. Inhibitory effect of selenomethionine on the
growth of three selected human tumor cell lines.
Redman C, Scott JA, Baines AT, Basye JL, Clark LC, Calley C,
Roe D, Payne CM, Nelson MA
Pharmacology/Toxicology Department, The University of
Arizona, Tucson 85724, USA.
Cancer Lett 1998 Mar 13;125(1-2):103-10
Selenium supplementation has been shown for many years to
work as an anticarcinogenic agent both in epidemiology and in
in vitro studies. Selenium supplementation has recently been
shown to decrease total cancer incidence. However, the
mechanism of action of selenium as an anticarcinogenic agent
has yet to be elucidated. Selenomethionine was the predominant
form of selenium in the dietary supplement in the study by
Clark et al. (Clark, L.C., Combs, G.F., Turnbull, W.B., Slate,
E.H., Chalker, D.K., Chow, J., Davis, L.S., Glover, R.A.,
Graham, G.F., Gross, E.G., Krongrad, A., Lesher, J.L., Park,
H.K., Sanders, B.B., Smith, C.L., Taylor, J.R. and The
Nutritional Prevention of Cancer Study Group (1996) Effects of
selenium supplementation for cancer prevention in patients
with carcinoma of the skin: a randomized controlled trial. J.
Am. Med. Assoc., 276 (24), 1957-1963) and therefore we
evaluated the growth inhibitory effects of selenomethionine
against human tumor cells. Selenomethionine was tested
against each of three human tumor cell lines (MCF-7/S breast
carcinoma, DU-145 prostate cancer cells and UACC-375 melanoma)
and against normal human diploid fibroblasts. All
cell lines demonstrated a dose-dependent manner of growth
inhibition by selenomethionine. Selenomethionine
inhibited the growth of all of the human tumor cell lines in
the micromolar (microM) range (ranging from 45 to 130 microM)
while growth inhibition of normal diploid fibroblasts required
1 mM selenomethionine, approximately 1000-fold higher than for
the cancer cell lines. In short, normal diploid
fibroblasts were less sensitive than the cancer cell lines to
the growth inhibitory effects of selenomethionine.
Furthermore, we show that selenomethionine administration to
these cancer cell lines results in apoptotic cell death and
aberrant mitoses. These results demonstrate the
differential sensitivity of tumor cells and normal cells to
selenomethionine.
136. Vitamins E plus C and interacting conutrients
required for optimal health. A critical and constructive
review of epidemiology and supplementation data regarding
cardiovascular disease and cancer.
Gey KF
Department of Biochemistry and Molecular Biology, University
of Berne, Switzerland.
Biofactors 1998;7(1-2):113-74
Antioxidants are crucial components of fruit/vegetable rich
diets preventing cardiovascular disease (CVD) and cancer:
plasma vitamins C, E, carotenoids from diet correlate
prevalence of CVD and cancer inversely, low levels predict an
increased risk of individuals which is potentiated by combined
inadequacy (e.g., vitamins C + E, C + carotene, A + carotene);
self-prescribed rectification of vitamins C and E at adequacy
of other micronutrients reduce forthcoming CVD, of vitamins A,
C, E, carotene and conutrients also cancer; randomized
exclusive supplementation of beta-carotene +/- vitamin A or E
lack benefits except prostate cancer reduction by vitamin E,
and overall cancer reduction by selenium; randomized
intervention with synchronous rectification of vitamins A + C
+ E + B + minerals reduces CVD and counteracts precancerous
lesions; high vitamin E supplements reveal potentials in
secondary CVD prevention. Plasma values desirable for primary
prevention: > or = 30 mumol/l lipid-standardized vitamin E
(alpha-tocopherol/cholesterol > or = 5.0 mumol/mmol); >
or = 50 mumol/l vitamin C aiming at vitamin C/vitamin E ratio
> 1.3-1.5; > or = 0.4 mumol/l beta- (> or = 0.5
mumol/l alpha+ beta-) carotene. CONCLUSIONS: In CVD vitamin E
acts as first risk discriminator, vitamin C as second one;
optimal health requires synchronously optimized vitamins C +
E, A, carotenoids and vegetable conutrients.
137. Serum and tissue lycopene and biomarkers of
oxidation in prostate cancer patients: a case-control
study.
Rao AV, Fleshner N, Agarwal S
Department of Nutritional Sciences, Faculty of Medicine,
University of Toronto, ON, Canada.
v.rao@utoronto.ca
Nutr Cancer 1999;33(2):159-64
Dietary intake of tomatoes and tomato products containing
lycopene, an antioxidant carotenoid, has been shown in recent
studies to reduce the risk of cancer. This study was conducted
to investigate the serum and prostate tissue lycopene and
other major carotenoid concentrations in cancer patients and
their controls. Serum lipid and protein oxidation was also
measured. Twelve prostate cancer patients and 12 age-matched
subjects were used in the study. Significantly lower
serum and tissue lycopene levels (44%, p = 0.04; 78%, p =
0.050, respectively) were observed in the cancer patients than
in their controls. Serum and tissue beta-carotene and
other major carotenoids did not differ between the two groups
(p = 0.395 and p = 0.280, respectively). Although there was no
difference (p = 0.760) in serum lipid peroxidation between
cancer patients and their controls (7.09 +/- 0.74 and 6.81 +/-
0.56 mumol/l, respectively), serum protein thiol levels were
significantly lower among the cancer patients (p = 0.026).
This study demonstrates that the status of lycopene but not
other carotenoids in prostate cancer patients is different
from controls. The role of dietary lycopene in
preventing oxidative damage of biomolecules and thereby
reducing the risk of prostate cancer needs to be evaluated in
future studies.
138. Chemoprevention for prostate cancer.
Brawer Michael K(a); Ellis William J
Seattle VA Med., Cent., 112 UR, 1660 South Columbian Way,
Seattle, WA 98108, USA
Cancer (Philadelphia) 75 (7 Suppl.):p1783-1789
1995
With prostate cancer representing the most common male
cancer and the second most common cause of cancer-related
death in men in the United States, increasing attention is
being directed at providing early detection, as well as
improvement in therapy. The third option to decrease
cancer-related deaths, decreasing the incidence, has only
recently gained attention. If tumor promoters can be removed
from the patient environment and/or agents administered that
inhibit cancer progression, we may indeed be able to decrease
the incidence of this most common neoplasm. The prostate is a
suitable site for chemoprevention strategies. High-risk
populations, including those men with a strong family history
of prostate cancer, black men, and/or men with prostatic
intraepithelial neoplasia, a putative premalignant change
identified on prostate biopsy or simple prostatectomy,
represent useful target populations. If a chemopreventive
strategy could be developed that was free of toxicity and also
simple, inexpensive, and readily administered, indeed all men
could be targeted. Several potential agents are available for
chemoprevention in the prostate. The retinoids
moderate differentiation and proliferation in several prostate
cell lines. Severe toxicity, however, may preclude
their widespread application. Difluoromethylornithine has also
been investigated. A chemopreventive trial directed
against lung cancer showed that alpha-tocopherol is associated
with a decreasing incidence of prostate cancer. The
greatest interest in the chemopreventive strategies for
prostate cancer, however, has focused on decreasing the male
androgens. Although most agents, such as luteinizing
hormone-releasing hormone agonists and antiandrogens, have
severe toxicity, the 5-alpha reductase inhibitors, because
they do not, are thought to be excellent agents for a
chemopreventive trial. The dependence of prostate epithelial
differentiation and maintenance of transformed cells on
circulating androgens is widely acknowledged. This is
the impetus for the hypothesis that reduction of circulating
androgens or blockage of testosterone to the more active
metabolite dihydrotestosterone by agents such as finasteride
or epristeride will reduce the incidence of prostate
cancer. The National Cancer Institute Intergroup
Prostate Cancer Prevention Trial, now underway, will randomize
18,000 men to receive 5 mg finasteride or a placebo daily for
7 years in a chemopreventive strategy. Entry requirements
include a normal result of digital rectal examination and a
serum prostate-specific antigen result less than 3.0 ng/ml.
Abnormalities on digital rectal examination results or
prostate-specific antigen level greater than 4.0 ng/ml on
annual evaluation indicate the need for biopsies in the men
receiving the placebo. An equal number of men will undergo
biopsy in the active arm of the study. At the end of the
7-year study, all men will have biopsies. Although the primary
endpoint is a reduction in prostate cancer incidence,
additional benefits include long-term follow-up of the
patients receiving finasteride, with potential salutary
benefits with regard to symptoms of benign prostatic
hyperplasia. This trial, which already has accrued more than
75% of the required participants, should resolve the issue of
whether reduction in effective androgen level will prevent the
development of prostate cancer.
139. Chemoprevention of prostate cancer: concepts
and strategies.
Kelloff GJ, Lieberman R, Steele VE, Boone CW, Lubet RA,
Kopelovitch L, Malone WA, Crowell JA, Sigman CC
National Cancer Institute, Division of Cancer Prevention,
Chemoprevention Branch, Bethesda, Md., USA.
Eur Urol 1999;35(5-6):342-50
Chemoprevention is the administration of agents to prevent
induction and inhibit or delay progression of cancers. For
prostate, as for other cancer targets, successful
chemopreventive strategies require well-characterized agents,
suitable cohorts, and reliable intermediate biomarkers of
cancer for evaluating chemopreventive efficacy. Agent
requirements are experimental or epidemiological data showing
chemopreventive efficacy, safety on chronic administration,
and a mechanistic rationale for the observed chemopreventive
activity. On this basis, promising chemopreventive
drugs in prostate include retinoids, antiandrogens,
antiestrogens, steroid aromatase inhibitors, 5alpha-reductase
inhibitors, vitamins D and E, selenium, lycopene, and
2-difluoromethylornithine. Phase II trials are
critical for evaluating chemopreventive efficacy. Cohorts in
these trials should be suitable for measuring the
chemopreventive activity of the agent and the intermediate
biomarkers chosen as endpoints. Many cohorts proposed for
phase II trials are patients with previous cancers or
premalignant lesions. For such patients, trials should be
conducted within the context of standard treatment. Two
cohorts currently used in phase II prostate cancer
chemoprevention trials are patients with PIN and patients
scheduled for prostate cancer surgery. Biomarkers should fit
expected biological mechanisms, be assayed reliably and
quantitatively, measured easily, and correlate to decreased
cancer incidence. Protocols for adequately sampling tissue are
essential. Changes in PIN provide prostate biomarkers with the
ability to be quantified and a high correlation to cancer. PIN
measurements include nuclear polymorphism, nucleolar size and
number of nucleoli/nuclei, and DNA ploidy. Other potentially
useful biomarkers are associated with cellular proliferation
kinetics (e.g. PCNA and apoptosis), differentiation (e.g.
blood group antigens, vimentin), genetic damage (e.g. LOH on
chromosome 8), signal transduction (e.g. TGFalpha, TGFbeta,
IGF-I, c-erbB-2 expression), angiogenesis, and biochemical
changes (e.g. PSA levels).
140. Diet, micronutrients, and the prostate
gland.
Thomas JA
Department of Pharmacology, University of Texas Health
Science Center, San Antonio, USA.
Nutr Rev 1999 Apr;57(4):95-103
Diseases of the prostate gland, particularly adenocarcinoma
and benign prostatic hyperplasia (BPH), are age-related.
Prostate cancer is the most commonly occurring tumor in U.S.
men. Differences in the incidence of this disease among ethnic
populations are not due solely to genetic differences. Many
efforts have been devoted to studying associations between
nutrition and prostate cancer. The strongest association
appears to be related to total fat intake and increased risk
of this malignancy. Evidence also exists to suggest a
role for certain micronutrients, such as zinc, selenium,
vitamin E, lycopene, phytoestrogens, and phytosterols,
although the role of nutrition and micronutrients in
protection against prostate cancer is less
convincing. Further research is necessary.
141. Lower prostate cancer risk in men with
elevated plasma lycopene levels: results of a prospective
analysis.
Gann PH, Ma J, Giovannucci E, Willett W, Sacks FM, Hennekens
CH, Stampfer MJ
Department of Preventive Medicine, Northwestern University
Medical School, Chicago, Illinois 60611, USA.
pgann@nwu.edu
Cancer Res 1999 Mar 15;59(6):1225-30
Dietary consumption of the carotenoid lycopene (mostly from
tomato products) has been associated with a lower risk of
prostate cancer. Evidence relating other carotenoids,
tocopherols, and retinol to prostate cancer risk has been
equivocal. This prospective study was designed to examine the
relationship between plasma concentrations of several major
antioxidants and risk of prostate cancer. We conducted a
nested case-control study using plasma samples obtained in
1982 from healthy men enrolled in the Physicians' Health
Study, a randomized, placebo-controlled trial of aspirin and
beta-carotene. Subjects included 578 men who developed
prostate cancer within 13 years of follow-up and 1294 age- and
smoking status-matched controls. We quantified the five major
plasma carotenoid peaks (alpha- and beta-carotene,
beta-cryptoxanthin, lutein, and lycopene) plus alpha- and
gamma-tocopherol and retinol using high-performance liquid
chromatography. Results for plasma beta-carotene are reported
separately. Odds ratios (ORs), 95% confidence intervals (Cls),
and Ps for trend were calculated for each quintile of plasma
antioxidant using logistic regression models that allowed for
adjustment of potential confounders and estimation of effect
modification by assignment to either active beta-carotene or
placebo in the trial. Lycopene was the only
antioxidant found at significantly lower mean levels in cases
than in matched controls (P = 0.04 for all cases). The ORs for
all prostate cancers declined slightly with increasing
quintile of plasma lycopene (5th quintile OR = 0.75, 95% CI =
0.54-1.06; P, trend = 0.12); there was a stronger inverse
association for aggressive prostate cancers (5th quintile OR =
0.56, 95% CI = 0.34-0.91; P, trend = 0.05). In the
placebo group, plasma lycopene was very strongly related to
lower prostate cancer risk (5th quintile OR = 0.40; P, trend =
0.006 for aggressive cancer), whereas there was no evidence
for a trend among those assigned to beta-carotene supplements.
However, in the beta-carotene group, prostate cancer risk was
reduced in each lycopene quintile relative to men with low
lycopene and placebo. The only other notable association was a
reduced risk of aggressive cancer with higher alpha-tocopherol
levels that was not statistically significant. None of the
associations for lycopene were confounded by age, smoking,
body mass index, exercise, alcohol, multivitamin use, or
plasma total cholesterol level. These results concur
with a recent prospective dietary analysis, which identified
lycopene as the carotenoid with the clearest inverse relation
to the development of prostate cancer. The inverse
association was particularly apparent for aggressive cancer
and for men not consuming beta-carotene supplements. For men
with low lycopene, beta-carotene supplements were associated
with risk reductions comparable to those observed with high
lycopene. These data provide further evidence that
increased consumption of tomato products and other
lycopene-containing foods might reduce the occurrence or
progression of prostate cancer.
142. Lycopene in association with alpha-tocopherol
inhibits at physiological concentrations proliferation of
prostate carcinoma cells.
Pastori M, Pfander H, Boscoboinik D, Azzi A
Institute for Biochemistry and Molecular Biology, University
of Bern, Bern, CH-3012, Switzerland.
Biochem Biophys Res Commun 1998 Sep
29;250(3):582-5
The effect of lycopene alone or in association with other
antioxidants was studied on the growth of two different human
prostate carcinoma cell lines (the androgen insensitive DU-145
and PC-3). It was found that lycopene alone was not a potent
inhibitor of prostate carcinoma cell proliferation.
However, the simultaneous addition of lycopene
together with alpha-tocopherol, at physiological
concentrations (less than 1 microM and 50 microM,
respectively), resulted in a strong inhibitory effect of
prostate carcinoma cell proliferation, which reached values
close to 90 %. The effect of lycopene with
alpha-tocopherol was synergistic and was not shared by
beta-tocopherol, ascorbic acid and probucol.
143. Study of prediagnostic selenium level in
toenails and the risk of advanced prostate cancer.
Yoshizawa K, Willett WC, Morris SJ, Stampfer MJ, Spiegelman
D, Rimm EB, Giovannucci E
Department of Nutrition, Harvard School of Public Health,
Boston, MA, USA.
J Natl Cancer Inst 1998 Aug 19;90(16):1219-24
BACKGROUND: In a recent randomized intervention trial, the
risk of prostate cancer for men receiving a daily supplement
of 200 microg selenium was one third of that for men receiving
placebo. By use of a nested case-control design within a
prospective study, i.e., the Health Professionals Follow-Up
Study, we investigated the association between risk of
prostate cancer and prediagnostic level of selenium in
toenails, a measure of long-term selenium intake.
METHODS: In 1986, 51,529 male health professionals aged
40-75 years responded to a mailed questionnaire to form the
prospective study. In 1987, 33,737 cohort members provided
toenail clippings. In 1988, 1990, 1992, and 1994, follow-up
questionnaires were mailed. From 1989 through 1994, 181 new
cases of advanced prostate cancer were reported. Case and
control subjects were matched by age, smoking status, and
month of toenail return. Selenium levels were determined by
neutron activation. All P values are two-sided.
RESULTS: The selenium level in toenails varied
substantially among men, with quintile medians ranging from
0.66 to 1.14 microg/g for control subjects. When
matched case-control data were analyzed, higher selenium
levels were associated with a reduced risk of advanced
prostate cancer (odds ratio [OR] for comparison of highest to
lowest quintile = 0.49; 95% confidence interval [CI] =
0.25-0.96; P for trend = .11). After additionally
controlling for family history of prostate cancer, body mass
index, calcium intake, lycopene intake, saturated fat intake,
vasectomy, and geographical region, the OR was 0.35 (95% CI =
0.16-0.78; P for trend = .03).
CONCLUSIONS: Our results support earlier findings
that higher selenium intakes may reduce the risk of prostate
cancer. Further prospective studies and randomized
trials of this relationship should be conducted.
144. Chemoprevention of prostate cancer: The
prostate cancer prevention trial.
Thompson Ian M(a); Coltman Charles A Jr; Crowley John
Dep. Surg., Brooke Army Med. Cent., 3851 Roger Brooke Dr.,
San Antonio, TX 78234-6200, USA
Prostate 33 (3):p217-221 Nov. 1, 1997
Background: A variety of innovative approaches to
the prevention of prostate cancer are now available, including
selenium, alpha tocopherol, dietary interventions, and vitamin
D. Perhaps the most promising opportunity is based
upon considerable evidence that cumulative androgen exposure
of the prostate contributes to the age-related risk of
prostate cancer.
Methods: The Prostate Cancer Prevention Trial has completed
randomization of over 18,000 healthy men to either finasteride
or placebo.
Conclusions: While the primary objective of this study is
to determine whether finasteride can reduce the period
prevalence of prostate cancer over a 7-year period, the
biologic and data resources of this study will provide
multiple opportunities to better understand this most common
cancer in U.S. men.
145. Effect of the lipidosterolic extract of
Serenoa repens (Permixon) and its major components on basic
fibroblast growth factor-induced proliferation of cultures of
human prostate biopsies.
Paubert-Braquet M; Cousse H; Raynaud JP; Mencia-Huerta JM;
Braquet P
Bio-Inova Euro Lab Research Laboratories, Plaisir,
France.
Eur Urol 1998;33(3):340-7
OBJECTIVE: To assess the effect of the lipidosterolic
extract of Serenoa repens (LSESr) on in vitro cell
proliferation in biopsies of human prostate
MATERIAL AND METHODS: Cell proliferation was assessed by
incorporation of [3H]thymidine followed by
historadiography.
RESULTS: Basic fibroblast growth factor (b-FGF) induced a
considerable increase in human prostate cell proliferation
(from +100 to +250%); the glandular epithelium was mainly
affected, minimal labeling being recorded in the other regions
of the prostate. Similar results were observed with epidermal
growth factor (EGF), although the increase in cell
proliferation was not recorded in some cases. Lovastatin, an
inhibitor of hydroxymethylglutaryl coenzyme A, antagonized
both the basal proliferation and the growth factor-stimulated
proliferation of human prostate epithelium (EGF, mean
inhibition approximately 80-95%; b-FGF, mean inhibition
approximately 40-90%). Geraniol, a precursor of both farnesyl
pyrophosphate and geranylgeranyl pyrophosphate, and farnesol,
the precursor of farnesyl pyrophosphate, increased cell
proliferation only in some prostate specimens, this effect
being antagonized by lovastatin. LSESr did not affect
basal prostate cell proliferation, with the exception of two
prostate specimens in which a significant inhibition of basal
proliferation was observed with the highest concentration of
LSESr (30 micrograms/ ml). In contrast, LSESr
inhibited b-FGF-induced proliferation of human prostate cell
cultures; this effect was significant for the highest
concentration of LSESr (30 micrograms/ml). In
some prostate samples, a similar inhibition was also
noted with lower concentrations. Unsaturated fatty
acids (UFA), in the range 1-30 ng/ml), did not affect the
basal prostate cell proliferation, only a slight increase in
cell proliferation was noted in 1 prostate specimen. UFA (1,
10 or 30 micrograms/ml) markedly inhibited the b-FGF-induced
cell proliferation down to the basal value. Lupenone,
hexacosanol and the unsaponified fraction of LSESr markedly
inhibited the b-FGF-induced cell proliferation, whereas a
minimal effect on basal cell proliferation was noted.
CONCLUSIONS: Despite the large variability in the response
of the prostate samples to b-FGF, these results
indicate that LSESr and its components affect the
proliferative response of prostate cells to b-FGF more than
their basal proliferation.
146. Efficacy and acceptability of tadenan (Pygeum
africanum extract) in the treatment of benign prostatic
hyperplasia (BPH): a multicentre trial in central
Europe.
Breza J; Dzurny O; Borowka A; Hanus T; Petrik R; Blane G;
Chadha-Boreham H
Department of Urology, University Hospital, Bratislava,
Slovak Republic.
Curr Med Res Opin (ENGLAND) 1998, 14 (3) p127-39
Pygeum africanum extract is available as Tadenan in many
countries, including those in central and eastern Europe, for
the treatment of mild to moderate BPH. Its efficacy and
acceptability have been demonstrated in numerous open and
placebo-controlled studies in large populations. The present
open three-centre efficacy and safety study was conducted
according to common protocol at urology clinics in the Czech
and Slovak Republics and in Poland, in order to confirm the
therapeutic profile of Pygeum africanum in conditions of daily
practice, using International Prostate Symptom Score (IPSS)
and flowmetry assessments. Men aged 50-75 years and in
compliance with the selection criteria (including IPSS > or
= 12, quality of life (QoL) score > or = 3, and maximum
urinary flow < or = 15 ml/s) were first examined then
recalled after two weeks during which no treatment was
provided (washout and check of stability). If still compliant,
they were entered at this point into a two-month period of
treatment with Pygeum africanum extract 50 mg twice daily.
There followed a further one-month period without treatment,
the objective being to evaluate the persistence of any effects
observed during the previous two months of Pygeum africanum
administration. The primary efficacy parameter investigated
was IPSS; the other efficacy parameters were QoL, nocturnal
frequency, maximum urinary flow, average urinary flow,
post-voiding residual volume and prostatic volume, after one
and two months of Pygeum africanum treatment and one month
after stopping treatment. A total of 85 patients were evenly
distributed between the three centres and completed the entire
study. At inclusion their mean IPSS was 16.17, QoL was 3.60
and nocturia was 2.6 times per night. The changes in
subjective scores, IPSS and QoL after the two-month treatment
period were highly statistically significant with mean
improvements of 40% and 31%, respectively. Nocturnal frequency
was reduced by 32% and the mean reduction was again highly
statistically significant. Mean maximum urinary flow, average
urinary flow and urine volume were also statistically
significantly improved, but the modest improvement in
post-voiding volume did not reach statistical significance.
The improvements, which exceeded those observed with placebo
in earlier studies, were maintained after one month without
treatment indicating an interesting persistence of clinically
useful activity. Prostatic volume and quality of sexual life
remained unchanged throughout. No treatment-related adverse
effects were observed. In conclusion, under conditions of
daily practice, Pygeum africanum extract induces
significant improvement in IPSS and uroflowmetry
parameters. These positive effects are accompanied by
a very satisfactory safety profile with the overall result of
a substantial improvement in QoL.
147. Review of recent placebo-controlled trials
utilizing phytotherapeutic agents for treatment of BPH
Lowe F.C.; Dreikorn K.; Borkowski A.; Braeckman J.; Denis L.;
Ferrari P.; Gerber G.; Levin R.; Perrin P.; Senge T.
Dr. F.C. Lowe, Department of Urology., St. Luke's/Roosevelt
Hospital, 425 West 59th St., 3A, New York, NY 10019 United
States
Prostate (United States) 1998, 37/3 (187-193)
BACKGROUND. In order to assess the efficacy of
phytotherapeutic agents for the treatment of benign prostatic
hyperplasia (BPH), a review of recently published double-blind
placebo-controlled trials was undertaken.
METHODS. Only those studies reviewed by the Other Medical
Therapies Committee of the Fourth International Consultation
on BPH were included.
RESULTS. These studies suggest a possible benefit for the
use of phytotherapeutic preparations in the treatment of
BPH.
CONCLUSIONS. These studies need to be confirmed in larger
long-term placebo-controlled studies in order to ascertain the
true efficacy of these agents.
148. Clinical relevance of growth factor
antagonists in the treatment of benign prostatic
hyperplasia
Desgrandchamps F.
Dr. F. Desgrandchamps, Department of Urology, Hopital
Saint-Louis, 1 avenue Claude Vellefaux, F-75475 Paris Cedex 10
France
European Urology (EUR. UROL.) (Switzerland) 1997, 32/SUPPL. 1
(28-31)
Changing demography and expectations about maintaining
quality of life mean that an increasing number of men will
require treatment for benign prostatic hyperplasia (BPH). Many
growth factors have a role in the development of BPH.
Consequently growth factor antagonists offer an attractive
therapeutic option. In double-blind randomised trials
Tadenan(R), a drug known to have growth factor
antagonist activity, conferred significant improvement of
urinary symptoms, maximum flow rate and residual volume, with
no serious side-effects. Therapeutic outcome could be
enhanced in a number of ways including matching patients with
particular cell type overgrowth for treatment with a growth
factor antagonist specific for that cell type. Full
exploitation of this approach awaits the development of less
invasive means of determining the cell type affected.
149. Cellular and molecular aspects of bladder
hypertrophy
Levin R.M.; Levin S.S.; Zhao Y.; Buttyan R.
Prof. R.M. Levin, Albany College of Pharmacy, Albany Medical
College, Stratton VA Medical Center, 106 New Scotland Avenue,
Albany, NY 12208-3492 United States
European Urology (Switzerland) 1997, 32/Suppl. 1
(15-21)
Bladder dysfunction secondary to benign prostatic
hyperplasia (BPH) is a major affliction associated with
ageing. As the disease slowly progresses, the bladder changes
from a state of compensation to decompensation, in which there
are severe, irreversible alterations in bladder function.
Using a rabbit model of partial outlet obstruction we have
identified three major cellular changes in the bladder which
result from such obstruction. These include progressive
denervation, mitochondrial dysfunction and disturbances of
calcium storage and release from the sarcoplasmic reticulum.
Our hypothesis is that outlet obstruction results in bladder
hypertrophy which induces ischaemia. This leads to a release
of intracellular calcium, leading to activation of specific
enzymes and generation of free radicals. These then attack the
membranes of nerves, sarcoplasmic reticulum and mitochondria.
We have demonstrated that pretreatment of rabbits with Pygeum
africanum extract (Tadenan(R)) significantly reduced the
severity of both the contractile and metabolic dysfunctions
induced by partial outlet obstruction. Our current
hypothesis is that Tadenan(R) may either prevent the
activation of degradative enzymes (or generation of free
radicals), or protect the intracellular membranes against the
destructive effects of free radicals or degredative
enzymes. In conclusion, identifying cellular
mechanisms responsible for bladder dysfunction induced by
partial outlet obstruction provides new possibilities for
non-surgical treatment of BPH. Our studies on
Tadenan(R) support this concept that the bladder provides a
novel target for therapeutic intervention.
150. Phytotherapy of benign prostatic hyperplasia
(BPH) with Cucurbita, Hypoxis, Pygeum, Urtica and Sabal
serrulata (Serenoa repens)
Odenthal K.P.
K.P. Odenthal, Dept. Exp. Biology, Pharmacology, MADAUS AG,
Ostmerheimerstr. 198, D-51109 Cologne Germany
Phytotherapy Research (United Kingdom) 1996, 10/Suppl. 1
(S141-S143)
The enlargement of prostate (BPH) is accompanied by urge,
reduced urinary flow and increased residual urine volume. The
etiology is not yet clear, though many results speak for
hormonal imbalance. Several herbal drugs have been applied
traditionally in the therapy of BPH, i.e., preparations of
Cucurbita, Hypoxis, Pygeum, Urtica and from Sabal serrulata.
Among the discussed mechanisms, phytosterols are considered as
active and have been found in experimental as well as in
clinical investigations to interfere with either reduction of
testosterone to dihydrotestosterone, sexual hormone binding
globulin, aromatization of testosterone or growth factors like
EGF. Additional effects have been documented in experiments
speaking for immunomodulation and anti-inflammatory qualities.
We demonstrate that smooth muscle contraction of rat
deferential duct, guinea-pig ileum and bladder is reduced by
lipophilic extract of Sabal. Both noradrenaline-induced
contractions of rat deferential duct as well as contractions
elicited by electrical stimulation could be reduced
concentration-dependently following addition of <= 0.33
mg/ml of lipophilic Sabal serrulata extract into the bath
medium. Cumulative dosing of <= 0.15 mg/ml of Sabal extract
antagonized in guinea-pig ileum and bladder smooth muscular
tissue contracted in KCl salt solution. Sabal extract, in
concentrations identical to those published for the so-called
anti-androgenic and anti-inflammatory effects, is therefore
characterized by alpha-adrenoceptor antagonistic as well as
calcium blocking activities. Furthermore, these findings could
explain the clinically demonstrated symptomatic relief or so
called release of dynamic component of BPH.
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