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From the * Department of Biological Sciences,
University of Notre Dame, Notre Dame, Indiana; the
Cell and Molecular Biology Program, University
College Dublin, Dublin, Ireland; and the
Trudeau Institute, Saranac Lake, New
York.
| Correspondence to: Dr Colm Morrissey, Department of Surgery, Mater Misercordiae Hospital, 47 Eccles St, Dublin 7, Ireland (e-mail: colm.morrissey.14{at}nd.edu ). |
| Received for publication July 13, 2001; accepted for publication November 20, 2001. |
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Abstract |
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Key words: Lipofuscin, antioxidants, stroma, age, hormone-dependent regression, apoptosis
-dihydrotestosterone
(5-DHT), which preferentially binds to the androgen receptor and is
most probably the only active androgen in the prostate
(Mainwaring, 1969; Tenniswood et al, 1982). The
reduction in prostate size that occurs after castration is primarily due to
the selective loss of the androgen-dependent secretory epithelial cells, which
undergo apoptosis (English et al,
1987). Since the stroma of the prostate does not require androgens
for survival, this results in a substantial change in the ratio of epithelial
and stromal cells. Since prostate cancer is a disease of the aging male, and the response to androgens, or androgen withdrawal, may be significantly influenced by age, we have compared the morphology of the ventral prostate, the effects of castration, the deposition of lipofuscin, and the expression of antioxidant enzymes in the ventral prostate of young and old Sprague-Dawley rats. A number of studies have examined different aspects of the aging process in the rodent prostate, including the development of hyperplasia and the propensity toward tumor formation, as well as biochemical and morphological changes (Shain et al, 1975, 1977; Shain and Boesel, 1977; Ichihara and Kawamura, 1979; Reznik et al, 1981; Pugh et al, 1994; Banerjee et al, 1998, 2000). Antioxidant enzymes such as catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase have been shown to display lobe-specific, age-related decreases in the rat prostate (Ghatak and Ho, 1996; Suzuki et al, 1997). The current study represents a systematic study of the effects of aging on the responsiveness of the prostate to hormone ablation and the changes in antioxidant enzymes that accompany aging.
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Materials and Methods |
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Trichrome Staining
Eight-micrometer frozen sections of ventral prostates were stained with
trichrome stain, processed according to the manufacturer (Poly Scientific
Research and Development Corp, Bay Shore, NY), and photographed using a Nikon
Optiphot-2 microscope.
Immunohistochemistry
Eight-micrometer frozen sections of ventral prostates were prepared on
gelatin-coated slides, fixed in 4% paraformaldehyde for 10 minutes, and washed
3 times in 10 mM phosphate-buffered saline (PBS). The sections were incubated
with mouse anticalponin 1/40 (Sigma Chemical Co, St Louis, Mo), mouse
antivimentin 1/40 (Sigma), mouse antichondroitin sulfate 1/40 (Sigma), rabbit
anti-manganese (Mn) superoxide dismutase 1/100 (StressGen Biotechnologies
Corp, Victoria, Canada), or rabbit anticatalase 1/100 (Abcam Ltd, Cambridge,
United Kingdom) in antibody buffer (3% [wt/vol] of bovine serum albumin, 0.3%
Triton X-100, in 10 mM PBS, pH 7.2) for 1 hour at room temperature and washed
3 times in 10 mM PBS. The sections were then incubated with either goat
anti-mouse 1/100 fluoresceinlabeled isothiocyanate secondary antibody (Sigma)
or donkey anti-rabbit Cy2 (Jackson Immunochemicals Laboratories Inc, West
Grove, Pa) at room temperature for 1 hour and washed 3 times in 10 mM PBS.
Slides were coverslipped with mounting medium (Vector Laboratories Inc,
Burlingame, Calif), and sections corresponding to the intermediate zone of the
prostatic ducts were photographed under indirect fluorescence. Control slides,
omitting the primary antibody, were run in parallel.
Autofluorescence
Eight-micrometer frozen sections of ventral prostates were prepared on
gelatin-coated slides, fixed in 4% paraformaldehyde for 10 minutes, and washed
3 times in 10 mM PBS. The sections were incubated with Hoechst dye (1 ng/mL),
mounted in Crystal/mount (Biomedia), and photographed under indirect
fluorescence.
Lipofuscin Staining With Sudan Black B
Eight-micrometer frozen sections of ventral prostate were immersed in 50%
ethanol for 5 minutes and in 70% ethanol for 5 minutes and were stained in a
saturated solution of Sudan Black B (Fisher Scientific, Pittsburgh, Pa) in 70%
ethanol at room temperature overnight. The sections were washed 3 times in 70%
ethanol and differentiated in a further wash in 70% ethanol for 10 minutes.
The sections were immersed in 50% and 30% ethanol washes for 5 minutes each,
washed in water, mounted in Crystal/mount, and photographed.
Oil Red O Staining
Eight-micrometer frozen sections of ventral prostate were covered with
absolute propylene glycol for 2 minutes and placed in 0.5% Oil Red O solution
in propylene glycol (Poly Scientific) overnight. The sections were
differentiated in 85% propylene glycol for 2 minutes, washed twice with water,
counterstained with Mayer Modified Hematoxylin (Poly Scientific) for 10
seconds, washed twice with water, mounted at 37°C with glycerine
jelly-mounting medium (Poly Scientific), and photographed.
Periodic Acid-Schiff Staining
Using the Harleco histochemical reaction set periodic acid-Schiff (PAS)
staining method (EM Diagnostic Systems, Gibbstown, NJ), 8-µm frozen
sections of ventral prostate were incubated with periodic acid for 10 minutes
and washed twice with water. The sections were incubated in Schiff reagent for
15 minutes, washed with water for 1 minute, and incubated in a working
solution of 20 mM Na2CO3 for 5 minutes. The sections
were washed once more in water and counterstained with Mayer Modified
Hematoxylin for 10 seconds. The sections were then washed in water, incubated
in a 0.5% NH4OH solution for 2 minutes, washed once more in water,
mounted in Crystal/mount, and photographed.
Electron Microscopy
Prostates excised from 3- and 12-month-old rats were placed in a petri dish
on ice containing 2% paraformaldehyde and 2.5% glutaraldehyde in 0.1 M sodium
cacodylate, pH 7.4, and were cut into approximately 1-mm3 pieces.
The tissue sections were incubated in fresh fixative at 4°C for several
weeks and were postfixed in 2% osmium tetroxide in 0.1 M sodium cacodylate, pH
7.4, at 4°C for 2 hours. The sections were washed twice for 10 minutes in
0.1 M sodium cacodylate, pH 7.4, and dehydrated by sequential 10-minute washes
in increasing ethanol concentrations: 30%, 50%, 70%, 80%, 95%, and 100%. The
tissues were infiltrated with 1:1 and with 3:1 Spurr:ethanol for 30 minutes
and placed in Spurr solution overnight (4-vinylcyclohexene dioxide, Dow epoxy
resin 736, nonenyl succinic anhydride, and dimethylaminoethanol [1 drop/mL]).
The following day, tissues were infiltrated with fresh Spurr solution for 30
minutes and embedded in Spurr solution and polymerized in the wells at
60°C overnight. The polymerized blocks were removed and stored until
sectioning on a Sorvall ultramicrotome. Sections (gold, approximately
850°) were floated onto nickel grids (Electron Microscopy Sciences, Fort
Washington, Pa), stained for 15 minutes in uranyl acetate, rinsed 3 times for
25 seconds in water, stained with lead citrate for 10 minutes, and rinsed 3
times each with 0.02 N NaOH and water. The grids were dried and then viewed
and photographed using a Hitachi H-600 transmission electron microscope.
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Results |
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In the 12-month-old animals, the prostate regresses much more slowly, such that 6 days after castration, the gland has decreased from 1164 plus or minus 238 mg to 706 plus or minus 208 mg, which is significantly larger than the gland in the intact young male. This corresponds to a decrease in the OW/BW ratio from 1.99 plus or minus 0.34 to 1.21 plus or minus 0.31. The OW/BW ratio does not change significantly in long-term castrates (data not shown), suggesting that the ventral prostate in old rats is significantly less sensitive to androgen ablation than in young rats.
Trichrome Staining
The majority of cells that line the lumen of the prostatic ducts in the
ventral prostates of young adult rats are tall columnar secretory epithelial
cells (Figure 2, Panel A).
There are numerous acinar projections into the lumen, and the stromal
component of the gland is minimal. Two days after castration, the majority of
epithelial cells are cuboidal, and only a few tall columnar epithelial cells
remain (Figure 2, Panel B). By
day 4, virtually all of the remaining epithelial cells are cuboidal and have a
significantly reduced cytoplasmic volume
(Figure 2, Panel C). The
stromal compartment is more evident, and the lumen of the ducts are
significantly smaller. By day 8, the epithelial cells form several layers
surrounding a very small lumenal space
(Figure 2, Panel D); in
addition, the stroma makes up a substantial proportion of the gland, the
smooth muscle cells surrounding the basement membrane are more evident, and
macrophage cells are visible.
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In the ventral prostates from older animals prior to castration, most of the lumen are significantly larger than those seen in young adults; however, there are very few acinar projections, and the majority of epithelial cells lining the ducts are cuboidal. Moreover, there are very few regions of the ducts that contain tall columnar epithelial cells (Figure 2, Panel E). After castration, the morphological changes in the prostate of old animals are far less dramatic than those seen in the young animals. Two days after castration, the lumen remain enlarged, and there are minimal changes in the stromal component of the gland. There are also very few acinar projections, and the majority of the epithelial cells lining the lumen are cuboidal (Figure 2, Panel F). Between 2 and 8 days after castration, the significant morphological change that is evident is the increase in the amount of stroma; however, this is not accompanied by any changes in the size of the lumen, which remain enlarged (Figure 2, Panels G and H).
Vimentin, Calponin, and Chondroitin Sulfate Immunohistochemistry
The morphological differences between the young and old rat ventral
prostates were further characterized using a variety of antibodies specific
for components of the extracellular matrix or cytoskeleton
(Figure 3). Vimentin is present
in the stromal compartment of the gland and is clearly visible in the acini of
the young animals (Figure 3,
Panel A). Staining is also present in the stromal compartment of the older
animals; however, there is a loss in the number and size of acini in the older
animals that is reflected by changes in the organization of vimentin
(Figure 3, Panel B). After
castration, the vimentin highlights the reorganization of the stroma in young
adults (Figure 3, Panel C),
while the lumen remain enlarged in the older animals, and the staining is not
significantly altered (Figure
3, Panel D).
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The differences in the ductal morphology between the young and old animals are further reflected by the organization of calponin in the smooth muscle cells surrounding the lumen within the gland (Figure 3, Panels E and F). Eight days after castration, the smooth muscle cells expressing calponin form a condensed sleeve around the lumenal epithelial cells in young animals (Figure 3, Panel G). In contrast, in the older animals, the ducts remain distended, and calponin organization is essentially unchanged (Figure 3, Panel H).
The expression of chondroitin sulfate highlights the changes in the extracellular matrix that accompany the loss of the acinar projections. In young animals, chondroitin sulfate is clearly localized in the basement membrane and within the acinar projections (Figure 3, Panel I), while staining varies in older animals (Figure 3, Panel J). After castration, the chondroitin sulfate is localized between the stroma and epithelial compartment in the younger animals, but the expression is significantly more variable, suggesting that the extracellular matrix undergoes significant proteolysis and reorganization (Figure 3, Panel K). In contrast, there is very little alteration in the localization of chondroitin sulfate in the older animals after castration (Figure 3, Panel L).
Changes in Autofluorescence During Regression
There is very little evidence of autofluorescent bodies in the ventral
prostates from young animals (Figure
4, Panel A). However, by day 8 after castration, in addition to
the strong autofluorescence of the stromal compartment, there are a number of
autofluorescent bodies in the surviving epithelial and macrophage cells
(Figure 3, Panel C). In
contrast, the epithelial cells of the ventral prostate from old rats contain
significant numbers of autofluorescent bodies even before castration
(Figure 3, Panel B), and by 8
days after castration, the surviving epithelial cells contain large, intensely
autofluorescent bodies; numerous macrophage cells also contain these bodies
(Figure 4, Panel D).
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The autofluorescent background of the stroma is not as obvious when compared to the younger day 8 castrates, since there is no major reorganization of the stroma in the older animals after castration.
Oil Red, Sudan Black, and PAS Staining of Lipofuscin
To verify that these autofluorescent antibodies are lipofuscin, we have
used a panel of 3 stains that recognize lipofuscin: Oil Red, Sudan Black, and
PAS. Intact ventral prostates from young and old animals were stained with Oil
Red and hematoxylin, PAS, and Sudan Black. The epithelial cells of the older
ventral prostates have cytoplasmic bodies that stain with Oil Red and Sudan
Black and are PAS positive (Figure
5, Panels D through F). The staining is highlighted by the arrows.
These bodies are not observed in the young animals
(Figure 5, Panels A through C).
These data suggest that autofluorescent bodies that are lipofuscin deposits
accumulate with age in the rat ventral prostate.
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Transmission Electron Microscopy of Lipofuscin
To further investigate the nature of the lipofuscin granules and their
localization within the epithelial cells of the aging rat ventral prostate, we
used transmission electron microscopy. Lipofuscin granules are generally not
observed in the tall columnar secretory epithelial cells in the young ventral
prostate (Figure 6, Panel A).
In the older rats, large lipofuscin granules are found in most of the tall
columnar secretory epithelial cells. These granules generally appear to be
supranuclear (Figure 6, Panel
B); however, some lipofuscin granules occasionally appear in the secretory
portion of the cells (data not shown). When compared to the ventral prostate
of younger rats, it is evident that lipofuscin accumulates with age in
perinuclear lipofuscin granules. Higher magnifications show the supranuclear
location of the lipofuscin granules and illustrate the complexity of these
granules. The granules appear as a dark electron-dense material, with what
appear to be large lipid droplets found randomly throughout the granule as
well as electron-dense domains that appear to be membrane bound
(Figure 6, Panel C).
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Antioxidant Enzyme Immunohistochemistry
Manganese superoxide dismutase stains intensely throughout the supranuclear
region of the secretory epithelial cells in the ventral prostate of young
animals (Figure 7, Panel A).
Four days after castration, Mn superoxide dismutase clearly localizes to a
region adjacent to the apical surface, possibly due to the reduction in the
cytoplasmic volume that occurs at this time
(Figure 7, Panel C). By day 8
after castration, the immunoreactivity has decreased very substantially, most
likely due to the loss of the tall columnar epithelial cells
(Figure 7, Panel E). In the
older animals, the staining of Mn superoxide dismutase is not as intense in
the intact prostate and is dispersed throughout the cytoplasm of the
epithelial cells (Figure 7,
Panel B); however, neither the localization nor the intensity changes
significantly after castration (Figure
7, Panels D and F).
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Catalase significantly is expressed at low levels in the epithelial cells of both young and old animals, with less staining in the older animals (Figure 7, Panels G and H). There is a transient increase in catalase staining in young animals on day 4 after castration that diminishes significantly by day 8, at which time the stain is seen sporadically throughout the tissue (Figure 7, Panels I and K). In older animals, the increase seen at day 4 after castration is maintained in the epithelial cells throughout the time course, and at day 8 after castration, the epithelial cells of the older animals express significant levels of catalase (Figure 7, Panels J and L).
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Discussion |
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TopAbstractMaterials and MethodsResultsDiscussionReferences |
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While it is well established that the columnar epithelial phenotype seen in
the ventral prostate of young animals is critically dependent on androgens
(Isaacs, 1984), it is not
clear which aspects of androgen action influence the stromal—epithelial
interactions or what aspect of these interactions changes in older animals.
Androgen action in the prostate is dependent on the conversion of testosterone
to 5-DHT by 5-reductase. 5-DHT has a high affinity for
the androgen receptor, and this interaction is required for the maintenance of
the epithelial morphology. Since, in the rat, endogenous serum testosterone
concentrations rise progressively until 12 months of age
(Berry and Isaacs, 1984), it is
unlikely that the changes in hormone responsiveness are attributable to the
absolute level of serum testosterone, which remains substantially above that
required to maintain a saturated receptor
(Berry and Isaacs, 1984). While
it is possible that the small changes in 5-reductase activity (which is
primarily localized in the stromal tissue) could influence the epithelial
cells, there is no evidence to demonstrate that these changes are of
sufficient magnitude to do so (Prins et
al, 1992). Numerous biochemical studies have demonstrated
significant differences in a number of enzyme activities with age
(Tenniswood et al, 1982;
Schultz and Shain, 1988; Goueli, 1990;
Quesada et al, 1990); however,
these studies have failed to take into consideration the changes in the
stromal/epithelial ratio or the substantial differences in tissue architecture
that accompany the aging process. It is therefore very difficult to determine
whether other well-characterized proteins play a significant role in
determining epithelial cell sensitivity to androgens or whether the relative
insensitivity of the older animals is due to as-yet unidentified epigenetic
factors.
The data presented in this paper demonstrate that the accumulation of lipofuscin in the tall columnar epithelial cells of the rat ventral prostate is age-dependent, although there is no equivalent accumulation in the stromal compartment. Lipofuscin is fluorescent under different wavelengths of light, including the red emission spectrum and, to a lesser extent, the ultraviolet and green emission spectra, and is recognized by lipophilic dyes and PAS stain. The autofluorescent properties of lipofuscin have been shown to differ among tissue types, suggesting that the constituents of lipofuscin vary from tissue to tissue (Mochizuki et al, 1995). Advanced glycation end products have physicochemical properties similar to those of lipofuscin and are known to colocalize with lipofuscin pigments in the brain (Horie et al, 1997) and macrophage cells (Ling et al, 1998). These data lead to the suggestion that lipofuscin is not only constituted of lipid peroxidation products but also of glycation products, which may be the origin of the fluorescent pigments (Horie et al, 1997; Kimura et al, 1998). Lipofuscin accumulation is not simply a linear function of age, but it also appears to be dependent on the specific metabolic rate (Sohal and Donato, 1978; Nakano and Gotoh, 1992; Moore et al, 1995). The origin of lipofuscin granules remains controversial. In some models, it appears to form within a lysosomal compartment due to peroxidative damage of autophagocytosed material that is not substantially eliminated from nondividing cells by degradation or exocytosis (Terman and Brunk, 1998). This would explain the accumulation of autofluorescent material in the macrophage cells in the regressing prostate by day 8 after castration in both 3-and 12-month-old animals, suggesting the autophagocytosed lipofuscin is retained by the macrophage cells and some surviving epithelial cells and is not eliminated. This represents an acute stimulus for the appearance of autofluorescent lipofuscin granules. However, the biogenesis of lipofuscin may occur under significantly more chronic conditions dependent on cell type and function. It has been suggested that lipofuscin is formed within a lysosomal compartment due to the production of hydrogen peroxide by mitochondria and other organelles, inducing lipid peroxidation and intermolecular cross-linking (Brunk et al, 1992). This may be the case in the aging prostate, where it appears to colocalize with lysosomal acid phosphatase in the epithelial cells (Aümuller and Seitz, 1985). Electron microscopy of the ventral prostate of the older rats shows that lipofuscin is contained within a supranuclear granule resembling those described by Ichihara and Kawamura (1979), who suggested that they represent an extension of the endoplasmic reticulum, as well as those by Harkin (1961), who described them as supranuclear ergastoplasmic sacs. The lipofuscin granules in the aging rat ventral prostate appear to be membrane bound and contain dark electron-dense material as well as what appear to be large lipid droplets. The supranuclear location suggests that these lipofuscin granules may be the accumulation of peroxidation and glycation products of the secretory pathway. In this context, these deposits may represent a compartment of the endoplasmic reticulum to which oxidized secretory proteins are shunted if they cannot be adequately degraded by proteolysis.
The accumulation of lipofuscin due to chronic oxidative damage or stress may be influenced by the antioxidant enzyme systems present in the cell (Lopez-Torres et al, 1993). It has been hypothesized that decreased activities or constitutive levels of oxidant repair enzymes may contribute to a progressive accumulation of oxidant damage with aging (Pacifici and Davies, 1991). The ability to mount an effective response to oxidative stress may decline with age, thus predisposing older cells and organisms to oxidative damage. Antioxidant enzymes such as catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase have been shown to display lobe-specific, age-related decreases in the Lobund-Wistar and Nobel rat prostate (Ghatak and Ho, 1996; Suzuki et al, 1997). In the young Sprague-Dawley rats, catalase is localized initially in the supernuclear cytoplasm of the secretory epithelial cells, while the Mn superoxide dismutase is expressed at high levels in the mitochondria of these cells. The expression of both of these enzymes is significantly diminished in the older animals. This is not simply due to the progressive loss of the tall columnar epithelial cells in the prostate but is also due to a decrease in the expression levels of the protein within the cuboidal cells of the gland. The differences in the antioxidant enzymes appear to correspond to the accumulation of oxidatively damaged cellular components such as lipofuscin, again suggesting that lipofuscin may be a marker for chronic oxidative stress (Sohal and Brunk, 1989).
However, the question remains whether there is any pathology associated with lipofuscin or whether lipofuscin is simply the byproduct of oxidative stress. While lipofuscin has been shown to be a photoinducible free radical generator leading to extragranular lipid peroxidation, enzyme inactivation, and protein oxidation (Wassell et al, 1999), it is not clear whether this photoinducible reaction can be mimicked by an interaction of lipofuscin with endogenous free radicals. Whether lipofuscin has any adverse effects on cell function through affecting the cytoarchitecture or causing oxidative damage remains to be determined.
The data presented in this paper suggest aging should be taken into account when drawing parallels between regression in the rat ventral prostate and the human prostate after hormonal ablation. These observations further suggest the ventral prostate from 12-month-old rats is a more pertinent model for the examination of current chemotherapeutic and hormonal therapies for prostate cancer.
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Acknowledgments |
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Footnotes |
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This work was published in part in the proceedings of the VII International Congress of Andrology.
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References |
|---|
|
TopAbstractMaterials and MethodsResultsDiscussionReferences |
|---|
Banerjee PP, Banerjee S, Lai JM, Strandberg JD, Zirkin BR, Brown
TR. Age-dependent and lobe-specific spontaneous hyperplasia in the brown
Norway rat prostate. Biol Reprod.
1998; 59:
1163
-1170.
Banerjee S, Banerjee PP, Brown TR. Castration-induced apoptotic
cell death in the brown Norway rat prostate decreases as a function of age.
Endocrinology.
2000; 141:
821
-832.
Berry SJ, Isaacs JT. Comparative aspects of prostatic growth and androgen metabolism with aging in the rat versus dog. Endocrinology. 1984; 114: 511 -520.[Abstract]
Brandes D. The fine structure and histochemistry of prostatic glands in relation to sex hormones. Int Rev Cytol. 1966; 20: 207 -276.[Medline]
Brunk UT, Jones CB, Sohal RS. A novel hypothesis of lipofuscinogenesis and cellular aging based on interactions between oxidative stress and autophagocytosis. Mutat Res. 1992; 275: 395 -403.[Medline]
Cunha GR, Donjacour AA, Cooke PS, Mee S, Bigsby RM, Higgins SJ, Sugimura Y. The endocrinology and developmental biology of the prostate. Endocr Rev. 1987; 8: 338 -362.[Medline]
English HF, Santen RJ, Isaacs JT. Response of glandular versus basal rat ventral prostatic epithelial cells to androgen withdrawal and replacement. Prostate. 1987; 11: 229 -242.[Medline]
Flickinger CJ. The fine structure of the interstitial tissue of the rat prostate. Am J Anat. 1972; 134: 107 -125.[Medline]
Ghatak S, Ho SM. Age-related changes in the activities of antioxidant enzymes and lipid peroxidation status in ventral and dorsolateral prostate lobes of noble rats. Biochem Biophys Res Commun. 1996;222: 362 -367.[Medline]
Goueli SA. Tissue-specific decline in cytosolic casein kinase II of the ventral prostate in aging rats. Prostate. 1990; 17: 113 -122.[Medline]
Harkin JC. Ultrastructural alterations with age in prostatic epithelial cells of the rat. Lab Invest. 1961; 10: 696 -706.[Medline]
Horie K, Miyata T, Yasuda T, Takeda A, Yasuda Y, Maeda K, Sobue G, Kurokawa K. Immunohistochemical localisation of advanced glycation end products, pentosidine, and carboxymethyllysine in lipofuscin pigments of Alzheimer's disease and aged neurons. Biochem Biophys Res Commun. 1997;236: 327 -332.[Medline]
Ichihara I, Kawamura H. The fine structure of ventral prostatic secretory epithelial cells in older rats. Cell Tissue Res. 1979;203: 181 -188.[Medline]
Isaacs JT. Antagonistic effect of androgen on prostatic cell death. Prostate. 1984;5: 545 -557.[Medline]
Kimura T, Takamatsu J, Miyata T, Miyakawa T, Horiuchi S. Localization of identified advanced glycation end-product structures, N epsilon(carboxymethyl)lysine and pentosidine, in age-related inclusions in human brains. Pathol Int. 1998; 48: 575 -579.[Medline]
Ling X, Sakashita N, Takeya M, Nagai R, Horiuchi S, Takahashi K. Immunohistochemical distribution and subcellular localization of three distinct specific molecular structures of advanced glycation end products in human tissues. Lab Invest. 1998; 78: 1591 -1606.[Medline]
Lopez-Torres M, Perez-Campo R, Fernandez A, Barba C, Barja De Quiroga G. Brain glutathione reductase induction increases early survival and decreases lipofuscin accumulation in aging frogs. J Neurosci Res. 1993;34: 233 -242.[Medline]
Mainwaring WI. The binding of (1,2-3H) testosterone within nuclei of the rat prostate. J Endocrinol. 1969; 44: 323 -333.[Medline]
Mochizuki Y, Park MK, Mori T, Kawashima S. The difference in autofluorescent features of lipofuscin between brain and adrenal. Zool Sci. 1995;12: 283 -288.[Medline]
Moore WA, Davey VA, Weinduch R, Walford R, Ivy GO. The effect of caloric restriction on lipofuscin accumulation in mouse brain with age. Gerontology. 1995; 41: 173 -185.
Nakano M, Gotoh S. Accumulation of cardiac lipofuscin depends on the metabolic rate of mammals. J Gerontol. 1992; 47: 126 -129.
Pacifici RE, Davies KJ. Protein, lipid and DNA repair systems in oxidative stress: the free-radical theory of aging revisited. Gerontology. 1991; 37: 166 -180.[Medline]
Prins GS, Cooke PS, Birch L, Donjacour AA, Yalcinkaya TM, Siiteri PK, Cunha GR. Androgen receptor expression and 5 alpha-reductase activity along the proximal-distal axis of the rat prostatic duct. Endocrinology. 1992; 130: 3066 -3073.[Abstract]
Pugh TD, Chang C, Uemura H, Weindruch R. Prostatic localization of
spontaneous early invasive carcinoma in Lobund-Wistar rats. Cancer
Res. 1994;54:
5766
-5770.
Quesada P, Faraone-Mennella MR, Jones R, Malanga M, Farina B. ADP-ribosylation of nuclear proteins in rat ventral prostate during aging. Biochem Biophys Res Commun. 1990; 170: 900 -907.[Medline]
Reznik G, Hamlin MH, Ward JM, Stinson SF. Prostatic hyperplasia and neoplasia in aging F344 rats. Prostate. 1981; 2: 261 -268.[Medline]
Rouleau M, Leger JG, Tenniswood MP. Ductal heterogeneity of cytokeratins, gene expression and cell death in the rat ventral prostate. Mol Endocrinol. 1990; 4: 2003 -2013.[Abstract]
Schultz JJ, Shain SA. Effect of aging on AXC/SSh rat ventral and dorsolateral prostate S-adenosyl-L-methionine decarboxylase and L-ornithine decarboxylase messenger ribonucleic acid content. Endocrinology. 1988; 122: 120 -126.[Abstract]
Shain SA, Boesel RW. Aging-associated diminished rat prostate androgen receptor co-concurrent with decreased androgen dependence. Mech Ageing Dev. 1977; 6: 219 -232.[Medline]
Shain SA, McCullough B, Nitchuk M, Boesel RW. Prostate carcinogenesis in the AXC rat. Oncology. 1977; 34: 114 -122.[Medline]
Shain SA, McCullough B, Segaloff A. Spontaneous adenocarcinomas of the ventral prostate of aged A X C rats. J Natl Cancer Inst. 1975;55: 177 -180.
Sohal R, Donato H. Effects of experimentally altered lifespans on the accumulation of fluorescent pigment in the housefly Musca domestica. Exp Gerontol. 1978; 13: 335 -341.[Medline]
Sohal RS, Brunk UT. Lipofuscin as an indicator of oxidative stress and aging. Adv Exp Med Biol. 1989; 266: 17 -29.[Medline]
Suzuki K, Oberley TD, Pugh TD, Sempf JM, Weindruch R. Caloric restriction diminishes the age-associated loss of immunoreactive catalase in rat prostate. Prostate. 1997; 33: 256 -263.[Medline]
Tenniswood M, Abrahams P, Winterton V, Bird CE, Clark AF. Binding of testosterone, 5 alpha-dihydrotestosterone and 5 alpha-androstane (3 alpha- and 3 beta-), 17 beta-diols to serum proteins in the rat. J Steroid Biochem. 1982;16: 617 -620.[Medline]
Terman A, Brunk UT. Ceroid/lipofuscin formation in cultured human fibroblasts: the role of oxidative stress and lysosomal proteolysis. Mech Ageing Dev. 1998; 104: 277 -291.[Medline]
Terry DE, Clark AF. Glycosaminoglycans in the three lobes of the rat prostate following castration and testosterone treatment. Biochem Cell Biol. 1996; 74: 653 -658.[Medline]
Wassell J, Davies S, Bardsley W, Boulton M. The photoreactivity of
the retinal age pigment lipofuscin. J Biol Chem.
1999; 274:
23828
-23832.
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