Journal of Molecular Histology

, Volume 39, Issue 4, pp 359–370 | Cite as

Expression of the ZNT (SLC30) family members in the epithelium of the mouse prostate during sexual maturation

  • Catherine P. Kirschke
  • Liping HuangEmail author
Original Paper


A prostate contains ~10-fold higher zinc than other soft organs. The function of the prostate is to produce a zinc-enriched seminal fluid. To establish a protein expression profile for zinc transporters involved in zinc efflux and intracellular sequestration/storage in the mouse prostate during sexual maturation, ZNT expression were investigated by immunohistochemistry. Our study demonstrated that ZNT proteins were differentially expressed in the prostate during sexual maturation. ZNT1 was mainly detected on the lateral membrane of the epithelium. Other ZNTs examined resided intracellularly. Among differences were a staining of ZNT2/ZNT5 in the ER-rich area of the epithelium in the anterior lobe, a staining of ZNT2 along the lateral and apical membrane, a luminal border staining of ZNT4, a staining of ZNT5 in the Golgi area of the epithelium in the ventral lobe, a uniform expression of ZNT6 across the lobes and ages, and a staining of ZNT7 in all lobes across ages.


Zinc transporters Slc30 family ZNT Mouse prostate Male genital tract Cellular zinc accumulation 



We special thank Dr. Shannon L. Kelleher of the Pennsylvania State University for the αZNT2 antibody. We thank Dr. Alexander Borowsky of the Center for Comparative Medicine, UC Davis, for technical support in identification of prostatic lobes. This work was supported by the United States Department of Agriculture CRIS:5306-515-30-014-00D and the NIH grant P60MD00222.


  1. Andrews GK, Wang H, Dey SK, Palmiter RD (2004) Mouse zinc transporter 1 gene provides an essential function during early embryonic development. Genesis 40:74–81. doi: 10.1002/gene.20067 PubMedCrossRefGoogle Scholar
  2. Beck FW, Prasad AS, Butler CE, Sakr WA, Kucuk O, Sarkar FH (2004) Differential expression of hZnT-4 in human prostate tissues. Prostate 58:374–381. doi: 10.1002/pros.10344 PubMedCrossRefGoogle Scholar
  3. Berquin IM, Min Y, Wu R, Wu H, Chen YQ (2005) Expression signature of the mouse prostate. J Biol Chem 280:36442–36451. doi: 10.1074/jbc.M504945200 PubMedCrossRefGoogle Scholar
  4. Black RE (1997) Zinc for child health. Child Health Res Project Spec Rep 1:1–24Google Scholar
  5. Brandes D, Portela A (1960a) The fine structure of the epithelial cells of the mouse prostate: I. Coagulating gland epithelium. J Biophys Biochem Cytol 7:505–509PubMedGoogle Scholar
  6. Brandes D, Portela A (1960b) The fine structure of the epithelial cells of the mouse prostate: II. Ventral lobe epithelium. J Biophys Biochem Cytol 7:511–514PubMedCrossRefGoogle Scholar
  7. Canale D, Bartelloni M, Negroni A, Meschini P, Izzo PL, Bianchi B et al (1986) Zinc in human semen. Int J Androl 9:477–480PubMedGoogle Scholar
  8. Chi ZH, Wang ZY, Wang X, Gao HL, Dahlstrom A, Huang L (2006) Zinc transporter 7 is located in the cis-Golgi apparatus of mouse choroid epithelial cells. Neuroreport 17:1807–1811. doi: 10.1097/01.wnr.0000239968.06438.c5 PubMedCrossRefGoogle Scholar
  9. Chimienti F, Devergnas S, Favier A, Seve M (2004) Identification and cloning of a beta-cell-specific zinc transporter, ZnT-8, localized into insulin secretory granules. Diabetes 53:2330–2337. doi: 10.2337/diabetes.53.9.2330 PubMedCrossRefGoogle Scholar
  10. Chimienti F, Devergnas S, Pattou F, Schuit F, Garcia-Cuenca R, Vandewalle B et al (2006) In vivo expression and functional characterization of the zinc transporter ZnT8 in glucose-induced insulin secretion. J Cell Sci 15:199–206Google Scholar
  11. Chowanadisai W, Lönnerdal B, Kelleher SL (2006) Identification of a mutation in SLC30A2 (ZnT-2) in women with low milk zinc concentration that results in transient neonatal zinc deficiency. J Biol Chem 281:39699–39707. doi: 10.1074/jbc.M605821200 PubMedCrossRefGoogle Scholar
  12. Costello LC, Franklin RB (1998) Novel role of zinc in the regulation of prostate citrate metabolism and its implications in prostate cancer. Prostate 35:285–296. doi:10.1002/(SICI)1097-0045(19980601)35:4<285::AID-PROS8>3.0.CO;2-FPubMedCrossRefGoogle Scholar
  13. Costello L, Franklin RB (2000) The intermediary metabolism of the prostate: a key to understanding the pathogenesis and progression of prostate malignancy. Oncology 59:269–282. doi: 10.1159/000012183 PubMedCrossRefGoogle Scholar
  14. Costello LC, Franklin RB (2006) The clinical relevance of the metabolism of prostate cancer; zinc and tumor suppression: connecting the dots. Mol Cancer 5:17. doi: 10.1186/1476-4598-5-17 PubMedCrossRefGoogle Scholar
  15. Cragg RA, Christie GR, Phillips SR, Russi RM, Küry S, Mathers JC et al (2002) A novel zinc-regulated human zinc transporter, hZTL1, is localized to the enterocyte apical membrane. J Biol Chem 277:22789–22797. doi: 10.1074/jbc.M200577200 PubMedCrossRefGoogle Scholar
  16. Dufner-Geattie J, Langmade SJ, Wang F, Eide D, Andrews GK (2003a) Structure, function, and regulation of a subfamily of mouse zinc transporter genes. J Biol Chem 278:50142–50150. doi: 10.1074/jbc.M304163200 CrossRefGoogle Scholar
  17. Dufner-Geattie J, Wang F, Kuo Y-M, Gitschier J, Eide D, Andrews GK (2003b) The acrodermatitis enteropathica gene ZIP4 encodes a tissue-specific, zinc-regulated zinc transporter in mice. J Biol Chem 278:33474–33481. doi: 10.1074/jbc.M305000200 CrossRefGoogle Scholar
  18. Eng BH, Guerinot ML, Eide D, Saier MH Jr (1998) Sequence analyses and phylogenetic characterization of the ZIP family of metal ion transport proteins. J Memebr Biol 166:1–7. doi: 10.1007/s002329900442 CrossRefGoogle Scholar
  19. Falcón-Pérez JM, Dell’Angelica EC (2007) Zinc transporter 2 (SLC30A2) can suppress the vesicular zinc defect of adaptor protein 3-depleted fibroblasts by promoting zinc accumulation in lysosomes. Exp Cell Res 313:1473–1483. doi: 10.1016/j.yexcr.2007.02.006 PubMedCrossRefGoogle Scholar
  20. Franklin RB, Ma J, Zou J, Guan Z, Kukoyi BI, Feng P et al (2003) Human ZIP1 is a major zinc uptake transporter for the accumulation of zinc in prostate cells. J Inorg Biochem 96:435–442. doi: 10.1016/S0162-0134(03)00249-6 PubMedCrossRefGoogle Scholar
  21. Franklin R, Feng P, Milon B, Desouki MM, Singh KK, Kajdacsy-Balla A et al (2005) hZIP1 zinc uptake transporter down regulation and zinc depletion in prostate cancer. Mol Cancer 4:32. doi: 10.1186/1476-4598-4-32 PubMedCrossRefGoogle Scholar
  22. Gaither LA, Eide DJ (2000) Functional expression of the human hZIP2 zinc transporter. J Biol Chem 275:5560–5564. doi: 10.1074/jbc.275.8.5560 PubMedCrossRefGoogle Scholar
  23. Gaither L, Eide DJ (2001) The human ZIP1 transporter mediates zinc uptake in human K562 erythroleukemia cells. J Biol Chem 276:22258–22264. doi: 10.1074/jbc.M101772200 PubMedCrossRefGoogle Scholar
  24. Huang L, Gitschier J (1997) A novel gene involved in zinc transport is deficient in the lethal milk mouse. Nat Genet 17:292–297. doi: 10.1038/ng1197-292 PubMedCrossRefGoogle Scholar
  25. Huang L, Kirschke CP, Gitschier J (2002) Functional characterization of a novel mammalian zinc transporter, ZnT6. J Biol Chem 277:26389–26395. doi: 10.1074/jbc.M200462200 PubMedCrossRefGoogle Scholar
  26. Huang L, Kirschke CP, Zhang Y, Yu Y-Y (2005) The ZIP7 gene (Slc39a7) encodes a zinc transporter involved in zinc homeostasis of the Golgi apparatus. J Biol Chem 280:15456–15463. doi: 10.1074/jbc.M412188200 PubMedCrossRefGoogle Scholar
  27. Huang L, Kirschke CP, Zhang Y (2006) Decreased intracellular zinc in human tumorigenic prostate epithelial cells: a possible role in prostate cancer progression. Cancer Cell Int 6:10. doi: 10.1186/1475-2867-6-10 PubMedCrossRefGoogle Scholar
  28. Jackson KA, Helston RM, McKay JA, O’Neill ED, Mathers JC, Ford D (2007) Splice variants of the human zinc transporter ZnT5 (SLC30A5) are differentially localized and regulated by zinc through transcription and mRNA stability. J Biol Chem 282:10423–10431. doi: 10.1074/jbc.M610535200 PubMedCrossRefGoogle Scholar
  29. Kambe T, Narita H, Yamaguchi-Iwai Y, Hirose J, Amano T, Sugiura N et al (2002) Cloning and characterization of a novel mammalian zinc transporter, zinc transporter 5, abundantly expressed in pancreatic β cells. J Biol Chem 277:19049–19055. doi: 10.1074/jbc.M200910200 PubMedCrossRefGoogle Scholar
  30. Kelleher SL, Lonnerdal B (2005) Zip3 plays a major role in zinc uptake into mammary epithelial cells and is regulated by prolactin. Am J Physiol Cell Physiol 288:C1042–C1047. doi: 10.1152/ajpcell.00471.2004 PubMedCrossRefGoogle Scholar
  31. Kerr WK, Keresteci AG, Mayoh H (1960) The distribution of zinc with the human prostate. Cancer 13:550–554. doi:10.1002/1097-0142(196005/06)13:3<550::AID-CNCR2820130320>3.0.CO;2-XPubMedCrossRefGoogle Scholar
  32. Kirschke CP, Huang L (2003) ZnT7, a novel mammalian zinc transporter, accumulates zinc in the Golgi apparatus. J Biol Chem 278:4096–4102. doi: 10.1074/jbc.M207644200 PubMedCrossRefGoogle Scholar
  33. Kvist U, Björndahl L, Kjellberg S (1987) Sperm nuclear zinc, chromatin stability, and male fertility. Scanning Microsc 1:1241–1247PubMedGoogle Scholar
  34. Liuzzi JP, Blanchard RK, Cousins RJ (2001) Differential regulation of zinc transporter 1, 2, and 4 mRNA expression by dietary zinc in rats. J Nutr 131:46–52PubMedGoogle Scholar
  35. Marker PC, Donjacoura AA, Dahiyab R, Cunha GR (2003) Hormonal, cellular, and molecular control of prostatic development. Dev Biol 253:165–174. doi: 10.1016/S0012-1606(02)00031-3 PubMedCrossRefGoogle Scholar
  36. Mawson CA, Fischer MI (1952) The occurrence of zinc in the human prostate gland. Can J Med Sci 30:336–339PubMedGoogle Scholar
  37. McMahon RJ, Cousins RJ (1998) Regulation of the zinc transporter ZnT-1 by dietary zinc. Proc Natl Acad Sci USA 95:4841–4846. doi: 10.1073/pnas.95.9.4841 PubMedCrossRefGoogle Scholar
  38. Michalczyk AA, Allen J, Blomeley RC, Ackland ML (2002) Constitutive expression of hZnT4 zinc transporter in human breast epithelial cells. Biochem J 15:105–113Google Scholar
  39. Murgia C, Vespignani I, Cerase J, Nobilo F, Perozzi G (1999) Cloning, expression, and vesicular localization of zinc transporter Dri 27/ZnT4 in intestinal tissue and cells. Am J Physiol 277:G1231–G1239PubMedGoogle Scholar
  40. Palmiter RD, Findley SD (1995) Cloning and characterization of a mammalian zinc transporter that confers resistance to zinc. EMBO J 14:639–649PubMedGoogle Scholar
  41. Palmiter R, Huang L (2004) Efflux and compartmentalization of zinc by members of the SLC30 family of solute carriers. Pflugers Arch Eur J Physiol 447:744–751CrossRefGoogle Scholar
  42. Palmiter R, Cole TB, Findley SD (1996a) ZnT-2, a mammalian protein that confers resistance to zinc by facilitating vesicular sequestration. EMBO J 15:1784–1791PubMedGoogle Scholar
  43. Palmiter R, Cole TB, Quaife CJ, Findley SD (1996b) ZnT-3, a putative transporter of zinc into synaptic vesicles. Proc Natl Acad Sci USA 93:14934–14939. doi: 10.1073/pnas.93.25.14934 PubMedCrossRefGoogle Scholar
  44. Sekler I, Moran A, Hershfinkel M, Dori A, Margulis A, Birenzweig N et al (2002) Distribution of the zinc transporter ZnT-1 in comparison with chelatable zinc in the mouse brain. J Comp Neurol 447:201–209. doi: 10.1002/cne.10224 PubMedCrossRefGoogle Scholar
  45. Singh J, Zhu Q, Handelsman DJ (1999) Stereological evaluation of mouse prostate development. J Androl 20:251–258PubMedGoogle Scholar
  46. Taylor K, Morgan HE, Johnson A, Nicholson RI (2004) Structure-function analysis of HKE4, a member of the new LIV-1 subfamily of zinc transporters. Biochem J 377:131–139. doi: 10.1042/BJ20031183 PubMedCrossRefGoogle Scholar
  47. Valentine RA, Jackson KA, Christie GR, Mathers JC, Taylor PM, Ford D (2007) ZnT5 variant B is a bidirectional zinc transporter and mediates zinc uptake in human intestinal Caco-2 cells. J Biol Chem 282:14389–14393. doi: 10.1074/jbc.M701752200 PubMedCrossRefGoogle Scholar
  48. Wang K, Zhou B, Kuo YM, Zemansky J, Gitschier J (2002) A novel member of a zinc transporter family defective in acrodermatitis enteropathica. Am J Hum Genet 71:66–73. doi: 10.1086/341125 PubMedCrossRefGoogle Scholar
  49. Yu YY, Kirschke CP, Huang L (2007) Immunohistochemical analysis of ZnT1, 4, 5, 6, and 7 in the mouse gastrointestinal tract. J Histochem Cytochem 55:223–234. doi: 10.1369/jhc.6A7032.2006 PubMedCrossRefGoogle Scholar
  50. Zaichick VY, Sviridova TV, Zaichick SV (1997) Zinc in the human prostate gland: normal, hyperplastic and cancerous. Int Urol Nephrol 29:565–574. doi: 10.1007/BF02552202 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  1. 1.USDA, ARSWestern Human Nutrition Research Center, UC DavisDavisUSA
  2. 2.Department of Nutrition and Rowe Program in GeneticsUniversity of California DavisDavisUSA

Personalised recommendations