Journal of Andrology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Iguchi, K.
Right arrow Articles by Hirano, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Iguchi, K.
Right arrow Articles by Hirano, K.
Journal of Andrology, Vol. 23, No. 6, November/December 2002
Copyright © American Society of Andrology

High-Level Expression of Zinc Transporter-2 in the Rat Lateral and Dorsal Prostate

KAZUHIRO IGUCHI*, SHIGEYUKI USUI*, TAKAHIRO INOUE{dagger}, YOSHIKI SUGIMURA{ddagger}, MASAE TATEMATSU§ AND KAZUYUKI HIRANO*

From the * Laboratory of Pharmaceutics, Gifu Pharmaceutical University, Mitahora-higashi, Gifu, Japan;{dagger} Department of Urology, Kyoto University Graduate School of Medicine, Shogoin, Kawara-cho, Sakyo-ku, Kyoto, Japan;{ddagger} Department of Urology, Mie University School of Medicine, Edobashi, Tsu, Mie, Japan; and§ Department of Tumor Pathology, Aichi Cancer Center Hospital, Kanokoden, Chikusa-ku, Nagoya, Japan.

Correspondence to: Dr Kazuyuki Hirano, Laboratory of Pharmaceutics, Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu 502-8585, Japan (e-mail: hirano{at}gifu-pu.ac.jp).
Received for publication May 23, 2002; accepted for publication February 4, 2002.

   Abstract
Top
 Abstract
Experimental Procedure
 Results
 Discussion
 References
 
Zinc is present at high concentrations in the prostate gland, however, the zinc-retention system in the prostate remains obscure. In this study, we investigated the expression of zinc transporters in the rat prostate and found that zinc transporter-2 (ZnT2), which sequesters zinc to the lysosome-like compartment, is expressed at high levels in the lateral prostate (LP) and dorsal prostate (DP), and that these areas contain higher levels of zinc than other tissues such as the ventral prostate (VP), liver, and kidney. Zinc levels in LP from castrated rats were lower than those in sham-operated rats. However, expression of ZnT2 in LP and DP was unaffected by castration. Expression of other zinc transporters (ZnT1, ZnT4, and divalent cation transporter 1) did not correlate with zinc levels. These results suggest that factors that regulate zinc homeostasis other than zinc transporters are involved in lowering zinc content after castration in rat prostate.

     Key words: Castration, lysosome, zinc


High concentrations of zinc, an essential trace element for most cells, are known to be retained in the prostate gland and secreted into the seminal plasma (Mawson and Fischer, 1951, 1952, 1953). Zinc is required for maintenance and activity of numerous metalloproteins, where it plays either a structural role or it has a catalytic function as part of the active sites of various metalloenzymes (Prasad, 1995; McCall et al, 2000). Zinc has also been suggested to have an antibacterial function in seminal plasma (Fair et al, 1976) and to be essential for optimal development and maintenance of the male reproductive system (Favier, 1992; Nishi, 1996). Recently, zinc was reported to control prostatic epithelial cell growth by inhibiting mitochondrial aconitase activities, cell cycle arrest, and induction of cell detachment (Costello and Franklin, 1981; Costello et al, 1997; Iguchi et al, 1998; Liang et al, 1999). Although the physiological functions of zinc in the prostate have been gradually revealed, the reason why zinc accumulates in the prostate remains unclear.

Many transporters that regulate zinc homeostasis have been identified in mammals. Divalent cation transporter 1 (DCT1) is a metal ion transporter that imports a variety of metal ions such as iron, zinc, cadmium, and copper from the extracellular environment into cells (Gunshin et al, 1997). Zinc transporter 1 (ZnT1), which was found by Palmiter et al (1996) using zinc-sensitive BHK cells, exports zinc out of cells to prevent zinc toxicity (Palmiter and Findley, 1995). ZnT2 is involved in zinc uptake into vesicles (endosome/lysosome compartment) in the intestine, kidney, and testis (Palmiter et al, 1996). ZnT4, which was identified using the positional cloning method, is also involved in zinc uptake into vesicles in the mammary gland, and was identified as the molecular basis of the recessive mouse mutation, "lethal milk syndrome" (Huang and Gitschier, 1997; Murgia et al, 1999). DCT1, ZnT1, and ZnT4 are ubiquitously expressed in most tissues, whereas ZnT2 displays tissue-restricted expression in rats.

The rat prostate consists of at least three anatomically independent lobes, designated as the ventral (VP), lateral (LP), and dorsal (DP) prostates. Biochemical compositions have been compared among these prostates. For example, VP was reported to secrete mainly citrate, polyamines, and spermine (Gerhardt et al, 1983). LP and DP were known to retain high levels of zinc in their lumen and epithelial cells (Chandler et al, 1977a,b; Sorensen et al, 1997). Moreover, the level of zinc was shown to decrease in LP, but to increase in VP following castration (Timms and Chandler, 1983; Yamashita et al, 1996; Liu et al, 1997). Although the level of zinc in the prostate is hormonally controlled, the mechanisms resulting in the above differences and the differential hormonal responsiveness among these lobes remain obscure.

Possible relationships between changes in zinc content in the prostate and prostatic diseases have been vigorously investigated. Zinc concentrations in the prostate gland were reported to be significantly lower in patients with prostatic cancer, and higher in those with benign prostatic hyperplasia, compared with levels in normal glands (Gyorkey et al, 1967; Ogunlewe and Osegbe, 1989). Zinc levels in seminal plasma of patients with bacterial prostatitis or sterility were observed to be consistently lower than those in healthy subjects (Fair et al, 1976; Nishi, 1996). Although functional disorder of zinc homeostasis seems to be associated with prostatic disease, it is unclear whether diseases cause the disruption of zinc homeostasis or vice versa.

In the present study, expression of zinc transporters in the rat prostate was examined by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) to clarify whether a zinc retention system by these transporters exists in the prostate. Elucidation of the zinc retention system in the prostate will be useful for investigating prostatic diseases.


   Experimental Procedure
Top
 Abstract
 Experimental Procedure
Results
 Discussion
 References
 
Animal Protocols

Animal protocols were approved by the Animal Care and Use Committee of Gifu Pharmaceutical University. Male Sprague-Dawley rats, 12 weeks old, were housed in an environmentally controlled room (25°C, 12 L:12 D cycle) and fed standard chow pellets and water ad libitum. Castration was performed surgically under Nembutal anesthetization via the scrotal route. Castrated and sham-operated rats were killed at 14 days postcastration and tissues were collected. The tissues were rapidly removed after rats were killed, and stored at -80°C until use.

Semiquantitative RT-PCR

Total cellular RNA was isolated using TRIzol reagent (Life Technologies, Inc, Rockville, Md) according to the manufacturer's instructions. Extracted RNA was dissolved in diethylpyro-carbonate (DEPC)-treated water and quantified by measuring the absorbance at 260 nm. Aliquots of 5 µg of total RNA were used to synthesize the first-strand complementary DNA (cDNA) with SuperScript II (Life Technologies) and subjected to PCR amplification with the oligonucleotide primers listed in Table 1 using a thermal cycler. The optimal PCR conditions were determined as the amount of amplification product in proportion to that of input RNA. PCR was performed under the following conditions: 26 cycles for 1 minute at 94°C, 1 minute at 57°C, and 1 minute at 72°C for ZnT1, ZnT2, and ZnT4; 27 cycles for 1 minute at 94°C, 1 minute at 59°C, and 1 minute at 72°C for DCT1; 24 cycles for 1 minute at 94°C, 1 minute at 58°C, and 1 minute at 72°C for glyceraldehyde-3-phosphate dehydrogenase (G3PDH). Control reactions for RT-PCR were performed by replacing the RNA sample with DEPC-treated water. G3PDH served as an internal RNA control to allow comparison of RNA levels among different specimens. After PCR, the reaction products were resolved on 1.75% agarose gels and visualized with ethidium bromide.


View this table:
[in this window]
[in a new window]
  		Table 1. Sequences of oligonucleotide primers for PCR
 

Tissue Preparation

Rat tissues were dissected and immediately frozen in liquid nitrogen to extract RNA. For other procedures, tissues were fractionated as described previously (Rowin, 1974; Compton and Witorsch, 1984). Briefly, tissues were pulverized, placed in 7 volumes of 0.25 M sucrose, and homogenized. The homogenate was centrifuged at 600 x g for 10 minutes and the resulting supernatant was then centrifuged at 3300 x g for 10 minutes. The precipitate obtained was resuspended in 0.25 M sucrose and designated as the heavy mitochondrial fraction. The supernatant was subsequently centrifuged at 25 000 x g for 10 minutes to obtain the pellet. This pellet was resuspended in 0.25 M sucrose and designated as the light mitochondrial fraction, which contained lysosomes. The resulting supernatant was further centrifuged at 100 000 x g for 60 minutes and the supernatant obtained was considered the cytosol. These fractions were used to determine the contents of zinc and the activity of acid phosphatase. For zinc assay with whole tissue, the samples were prepared using 7 volumes of Milli-Q water (Millipore Corp, Bedford, Mass) instead of 0.25 M sucrose. Protein concentrations were determined by the Bradford assay (Bradford, 1976) using bovine serum albumin as a standard.

Zinc Assay

Zinc was assayed by atomic absorption as described previously (Liu et al, 1997), after samples were digested in trichloroacetic acid/nitric acid (50/50) solution in a boiling water bath for 30 minutes.

Acid Phosphatase Activity

Acid phosphatase activity was assayed according to the method described by Kind and King (1954) and expressed as King-Armstrong units per milligram of protein.

Statistical Analysis

The significance of differences between groups was calculated using the Student t-test.


   Results
Top
 Abstract
 Experimental Procedure
 Results
Discussion
 References
 
Expression of Zinc Transporters in Rat Tissues

Zinc levels in the prostate and other tissues are presented in Figure 1. The results demonstrated that zinc levels in LP and DP were approximately 30-fold and 4-fold higher, respectively, than those in other tissues. The zinc level in VP was nearly the same as levels in kidney and liver (Figure 1).



View larger version (13K):
[in this window]
[in a new window]
  		Figure 1. Zinc levels in different tissues of normal rats. Total zinc levels of tissues were determined as described in "Experimental Procedure." Values are expressed as means ± SD of 8 animals. *P < .05 versus values obtained in kidney.

 

To determine what kinds of transporters are involved in the zinc transport system in the rat prostate gland, expression levels of zinc transporters were examined by semiquantitative RT-PCR. ZnT1, ZnT2, ZnT4, and DCT1 were chosen as candidates of the transporters because expression of these factors has been identified in rats. As shown in Figure 2, ZnT2 messenger RNA (mRNA) was expressed at higher levels in LP and DP than it was in other tissues, and ZnT4 mRNA expression in VP was found to be highest in three anatomically independent lobes of the prostate. The sample RNAs that had not been reverse-transcribed did not yield a PCR product (data not shown).



View larger version (47K):
[in this window]
[in a new window]
  		Figure 2. RT-PCR analysis of zinc transporter mRNA expression in rat tissues. Total RNA was purified from rat tissues and subjected to RT-PCR. The products were resolved on 1.75% agarose gels and visualized with ethidium bromide. Data shown are representative of at least 3 animals.

 

Because ZnT2 is known to transport zinc into lysosomes (Palmiter et al, 1996), zinc is expected to accumulate in lysosomes of LP and DP in which ZnT2 was observed to be expressed at high levels. Therefore, zinc amounts, together with those of acid phosphatase, which is considered a lysosomal marker enzyme, were determined after subcellular fractionation of tissues. As shown in Table 2, acid phosphatase activity was predominantly detected in the light mitochondrial fractions of all tissues listed and was lowest in all cytosolic fractions among the three subcellular fractions, except that the activity in the subcellular fractions of LP was quite low. This low activity may have been due to the inhibitory effects of high levels of zinc in LP as described below, because zinc ions are known to inhibit the activity of acid phosphatase (DeChatelet et al, 1971). Thus, the fractionation was judged to be sufficient. As shown in Table 3, DP zinc levels in the heavy mitochondrial fraction and the light mitochondrial fraction, which contained lysosomes, were about threefold higher than that in the cytosolic fraction. The zinc level in the light mitochondrial fraction from LP was slightly higher than it was in the heavy mitochondrial and cytosolic fractions, but the differences were not significant. This probably represents the contamination of the cytosolic fraction in LP with zinc from the lumen, because our method was unable to separate zinc from the epithelial cells and lumen. On the other hand, zinc levels in the light mitochondrial fraction from VP, liver, and kidney were no higher than those in the heavy mitochondrial and cytosolic fractions.


View this table:
[in this window]
[in a new window]
  		Table 2. Acid phosphatase activity in subcellular fractions of various rat tissuesa
 

View this table:
[in this window]
[in a new window]
  		Table 3. Subcellular distribution of zinc in rat tissuesa
 

Expression of Zinc Transporters in Castrated Rat Tissues

Zinc levels in various tissues from castrated and sham-operated rats are presented in Table 4. The level of zinc in LP from castrated rats was significantly lower than it was in sham-operated rats. On the other hand, zinc levels in VP of castrated rats was twofold higher than it was in sham-operated rats. No significant differences in zinc content of the other tissues were observed after castration.


View this table:
[in this window]
[in a new window]
  		Table 4. Effect of castration on zinc contents in rat tissuesa
 

Because hormone manipulation is known to regulate the zinc level in the prostate, expression levels of zinc transporters in castrated and sham-operated rats were investigated. As shown in Figure 3, although ZnT2 mRNA expression in LP was not affected by castration, its expression in VP was slightly increased. Messenger RNA expression of the other transporters examined was unaffected by castration.



View larger version (60K):
[in this window]
[in a new window]
  		Figure 3. Effect of castration on mRNA expression of zinc transporters. Total RNA was purified from castrated and sham-operated rat tissues. Messenger RNA expression of zinc transporters was examined with semiquantitative RT-PCR. The products were resolved on 1.75% agarose gels and visualized with ethidium bromide. Data shown are representative for at least 3 animals.

 


   Discussion
Top
 Abstract
 Experimental Procedure
 Results
 Discussion
References
 
In the present study, we demonstrated that high levels of ZnT2 mRNA were expressed in LP and DP, and we also showed that the lysosome-rich subcellular fraction contained a higher concentration of zinc than the other fractions. ZnT2 has been reported to be localized in the lysosomes and to sequester zinc into the vesicular compartments based on the observation of colocalization of ZnT2/green fluorescent fusion protein with Lyso Tracker (Molecular Probes, Eugene, Ore) and acridine orange, endosomal/lysosomal fluorescent dyes (Palmiter et al, 1996). Moreover, the lysosome-like compartment in rat LP was shown to contain a high level of zinc by x-ray microanalysis (Chandler et al, 1977a,b; Sorensen et al, 1997). These observations and our results indicate that ZnT2 in LP and DP sequesters intracellular zinc to the lysosome-like compartment.

Accumulation of zinc in the prostate has been reported to be regulated by hormones in vivo and in vitro. Animal experiments showed that administration of testosterone and prolactin raised zinc levels in LP, and lowered them in VP. In contrast, our results (shown in Table 4) and previous reports showed that castration lowered zinc levels in LP and raised them in VP (Timms and Chandler, 1983; Yamashita et al, 1996; Liu et al, 1997). Moreover, in vitro studies have revealed that testosterone and prolactin regulate the zinc transport system in human prostatic LNCaP and PC-3 cells (Costello et al, 1999). From these observations, we first suspected that ZnT2, which is highly expressed in LP and DP, was under hormonal control. In the present study, however, with androgen ablation, no significant changes in ZnT2 mRNA expression were observed in LP or DP, where most zinc is present, although zinc levels were lower in the prostate. Therefore, ZnT2 expression would not be involved in the decrease of zinc levels in the prostate of castrated rats.

Although ZnT2 expression in LP and DP was not changed by castration, a significant increase in its mRNA expression was observed in VP. The number of epithelial cells is known to be significantly lowered by castration in VP compared with those in LP and DP (Kiplesund et al, 1988). If the difference in ZnT2 expression levels is found between epithelial cells and stromal cells, the shift in the cellular ratio by castration may affect the change in ZnT2 mRNA expression observed in VP. Moreover, because the androgen receptor was reported to be abundantly expressed in VP compared with LP and DP (Prins, 1989), then VP is generally more susceptible to hormones than the other parts of prostate and requires androgens for its morphological and functional maintenance. The expression of ZnT2 mRNA in VP may be at least in part inhibited by androgens.

We also found that higher levels of ZnT4 mRNA were expressed in VP than in LP and DP. ZnT4 is known to be localized in the membrane of intracellular vesicles and to sequester zinc into the vesicular compartments (Murgia et al, 1999). A single point mutation in ZnT4 was demonstrated to result in lethal milk syndrome (Huang and Gitschier, 1997). The milk produced by homozygous ZnT4 mutant females contains insufficient zinc to support the needs of growing mice pups. ZnT4 in VP might be involved in the secretory role of zinc into the seminal plasma in a manner similar to ZnT4 in the mammary gland, where ZnT4 is presumed to secrete zinc into the milk. Lower levels of zinc in seminal plasma were found in patients with prostatitis or sterility (Fair et al, 1976; Nishi, 1996). ZnT4 expression levels in these patients are expected to be determined in future studies.

In this study, high levels of zinc were observed in not only the light mitochondrial fraction, which contains lysosomes, but also in the heavy mitochondrial fraction in DP. Franklin et al demonstrated that accumulation of high levels of zinc in the mitochondria of prostate cells inhibited mitochondrial aconitase activity (Costello and Franklin, 1981; Costello et al, 1997). Inhibition of aconitase activity, which regulates ATP production, suppressed the growth of prostatic epithelial cells. Thus, the role of mitochondrial zinc in the prostate is being clarified. On the other hand, no information is available at present concerning the high levels of zinc in lysosomes and its regulation in the prostate. Zinc in lysosomes is known to mediate stabilization of the lysosomal membrane (Chvapil et al, 1972), to modify various enzyme activities (DeChatelet et al, 1971; Shin and Mego, 1988; Hiraiwa et al, 1993), and to modify intracellular cholesterol transport (Kobayashi et al, 1999). These functions may affect the roles of zinc in the lysosomes in the prostate.

Zinc levels in VP were nearly the same as those in the kidney and liver (Figure 1), whereas Liu et al (1997) reported that zinc levels in VP were approximately three-fold higher than those in the kidney and liver. This discrepancy might be explained by contamination by serum zinc because liver and kidney perfusion were not carried out in our experiments.

In conclusion, this is the first report of the observation of ZnT2 mRNA in rat LP and DP. In addition, no androgenic regulation of ZnT2 mRNA was found in LP or DP. Changes in zinc concentration in prostatic diseases have been well defined. Although ZnT2 expression was suggested to be unrelated to changes in zinc levels in the prostate of castrated rats, clarification of the relationship between ZnT2 expression and prostatic diseases might help in understanding the physiology of the prostate.


   References
Top
 Abstract
 Experimental Procedure
 Results
 Discussion
 References
 
Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem.1976; 72:248 -254.[Medline]

Chandler JA, Sinowatz F, Timms BG, Pierrepoint CG. The subcellular distribution of zinc in dog prostate studied by x-ray microanalysis. Cell Tissue Res.1977a; 185:89 -103.[Medline]

Chandler JA, Timms BG, Morton MS. Subcellular distribution of zinc in rat prostate studied by x-ray microanalysis: I. Normal prostate. Histochem J.1977b; 9:103 -120.[Medline]

Chvapil M, Ryan JN, Zukoski CF. The effect of zinc and other metals on the stability of lysosome. Proc Soc Exp Biol Med.1972; 140:642 -646.[Medline]

Compton MM, Witorsch RJ. Proteolytic degradation and modification of rat prolactin by subcellular fractions of the rat ventral prostate gland. Endocrinology.1984; 115:476 -484.[Abstract]

Costello LC, Franklin RB. Aconitase activity, citrate oxidation, and zinc inhibition in rat ventral prostate. Enzyme.1981; 26:281 -287.[Medline]

Costello LC, Liu Y, Zou J, Franklin RB. Evidence for a zinc uptake transporter in human prostate cancer cells which is regulated by prolactin and testosterone. J Biol Chem.1999; 274:17499 -17504.[Abstract/Free Full Text]

Costello LC, Liu Y, Franklin RB, Kennedy MC. Zinc inhibition of mitochondrial aconitase and its importance in citrate metabolism of prostate epithelial cells. J Biol Chem.1997; 272:28875 -28881.[Abstract/Free Full Text]

DeChatelet LR, Cooper MR, McCall CE. Studies on leukocyte phosphatases. 3. Inhibition of leukocyte acid phosphatase by zinc. Clin Chem.1971; 17:1176 -1179.[Abstract]

Fair WR, Couch J, Wehner N. Prostatic antibacterial factor. Urology. 1976;7:169 -177.[Medline]

Favier AE. The role of zinc in reproduction. Hormonal mechanisms. Biol Trace Elem Res.1992; 32:363 -382.[Medline]

Gerhardt PG, Mevag B, Tveter KJ, Purvis K. A systematic study of biochemical differences between the lobes of the rat prostate. Int J Androl. 1983;6:553 -562.[Medline]

Gunshin H, Mackenzie B, Berger UV, et al. Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature. 1997;388:482 -487.[Medline]

Gyorkey F, Min K, Huff JA, Gyorkey P. Zinc and magnesium in human prostate gland: normal, hyperplastic, and neoplastic. Cancer Res. 1967;27:1348 -1353.[Medline]

Hiraiwa M, Yamauchi T, Tsuji S, Nishizawa M, Miyatake T, Oyanagi K, Ikuta F, Uda Y. Activation of human lysosomal sialidase. J Biochem. 1993;114:901 -905.[Abstract/Free Full Text]

Huang L, Gitschier J. A novel gene involved in zinc transport is deficient in the lethal milk mouse. Nat Genet.1997; 17:292 -297.[Medline]

Iguchi K, Hamatake M, Ishida R, et al. Induction of necrosis by zinc in prostate carcinoma cells and identification of proteins increased in association with this induction. Eur J Biochem.1998; 253:766 -770.[Medline]

Kind PRN, King EJ. Estimation of plasma phosphatase by determination of hydrolyzed phenol with aminoantipyrine. J Clin Pathol. 1954;7:332 -336.

Kiplesund KM, Halgunset J, Fjosne HE, Sunde A. Light microscopic morphometric analysis of castration effects in the different lobes of the rat prostate. Prostate.1988; 13:221 -232.[Medline]

Kobayashi T, Beuchat MH, Lindsay M, Farias S, Palmiter RD, Sakuraba H, Parton RG, Gruenberg J. Late endosomal membranes rich in lysobisphosphatidic acid regulate cholesterol transport. Nat Cell Biol. 1999;1:113 -118.[Medline]

Liang Y, Liu Y, Zou J, Franklin RB, Costello LC, Feng P. Inhibitory effect of zinc on human prostatic carcinoma cell growth. Prostate. 1999;40:200 -207.[Medline]

Liu Y, Franklin RB, Costello LC. Prolactin and testosterone regulation of mitochondrial zinc in prostate epithelial cells. Prostate. 1997;30:26 -32.[Medline]

Mawson CA, Fischer MI. Zinc content of the genital organs of the rat. Nature.1951; 167:859 .

Mawson CA, Fischer MI. The occurrence of zinc in the human prostate gland. Can J Med Sci.1952; 30:336 -339.

Mawson CA, Fischer MI. Zinc and carbonic anhydrase in human semen. Biochem J.1953; 55:696 -700.[Medline]

McCall KA, Huang C-C, Fierke CA. Function and mechanism of zinc metalloenzymes. J Nutr.2000; 130:1437S -1446S.[Abstract/Free Full Text]

Murgia C, Vespognani I, Cerase J, Nobio N, Perozzi G. Cloning, expression, and vesicular localization of zinc transporter Dri 27/ZnT4 in intestinal tissue and cells. Am J Physiol.1999; 277:G1231 -G1239.

Nishi Y. Zinc and growth. J Am Coll Nutr.1996; 15:340 -344.[Abstract]

Ogunlewe JO, Osegbe DN. Zinc and cadmium concentrations in indigenous blacks with normal, hypertrophic, and malignant prostate. Cancer. 1989;63:1388 -1392.[Medline]

Palmiter RD, Cole TB, Findley SD. ZnT-2, a mammalian protein that confers resistance to zinc by facilitating vesicular sequestration. EMBO J. 1996;15:1784 -1791.[Medline]

Palmiter RD, Findley SD. Cloning and functional characterization of a mammalian zinc transporter that confers resistance to zinc. EMBO J. 1995;14:639 -649.[Medline]

Prasad AS. Zinc: an overview. Nutrition.1995; 11:93 -99.[Medline]

Prins GS. Differential regulation of androgen receptors in the separate rat prostate lobes: androgen independent expression in the lateral lobe. J Steroid Biochem.1989; 33:319 -326.[Medline]

Rowin GL. Isolation of lysosomes. In: Laskin AI, Last JA, eds. Subcellular Particles, Structures and Organelles. New York: Marcel-Dekker; 1974:89 -109.

Shin HJ, Mego JL. A rat liver lysosomal membrane flavin-adenine dinucleotide phosphohydrolase: purification and characterization. Arch Biochem Biophys.1988; 267:95 -103.[Medline]

Sorensen MB, Stoltenberg M, Juhl S, Danscher G, Ernst E. Ultrastructural localization of zinc ion in the rat prostate: an autometallographic study. Prostate.1997; 31:125 -130.[Medline]

Timms BG, Chandler KA. Effects of androgens on the ultrastructure and subcellular zinc distribution in the prostatic epithelium of castrated rats. Prostate.1983; 4:57 -72.[Medline]

Yamashita A, Hayashi N, Sugimura Y, Cunha GR, Kawamura J. Influence of diethylstilbestrol, Leuprolein (a luteinizing hormone-releasing hormone analog), Finasteride (a 5{alpha}-reductase inhibitor), and castration on the lobar subdivisions of the rat prostate. Prostate1996; 29:1 -14.[Medline]




This article has been cited by other articles:


Home page
 J. Leukoc. Biol.Home page
S. Overbeck, P. Uciechowski, M. L. Ackland, D. Ford, and L. Rink
Intracellular zinc homeostasis in leukocyte subsets is regulated by different expression of zinc exporters ZnT-1 to ZnT-9
J. Leukoc. Biol., February 1, 2008; 83(2): 368 - 380.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. P. Liuzzi, J. A. Bobo, L. A. Lichten, D. A. Samuelson, and R. J. Cousins
Responsive transporter genes within the murine intestinal-pancreatic axis form a basis of zinc homeostasis
PNAS, October 5, 2004; 101(40): 14355 - 14360.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Iguchi, K.
Right arrow Articles by Hirano, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Iguchi, K.
Right arrow Articles by Hirano, K.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS