Advertisement

Gender differences in kidney function

  • Ivan SabolićEmail author
  • Abdul R. Asif
  • Wolfgang E. Budach
  • Christoph Wanke
  • Andrew Bahn
  • Gerhard Burckhardt
Invited Review

Abstract

Sex hormones influence the development of female (F) and male (M) specific traits and primarily affect the structure and function of gender-specific organs. Recent studies also indicated their important roles in regulating structure and/or function of nearly every tissue and organ in the mammalian body, including the kidneys, causing gender differences in a variety of characteristics. Clinical observations in humans and studies in experimental animals in vivo and in models in vitro have shown that renal structure and functions under various physiological, pharmacological, and toxicological conditions are different in M and F, and that these differences may be related to the sex-hormone-regulated expression and action of transporters in the apical and basolateral membrane of nephron epithelial cells. In this review we have collected published data on gender differences in renal functions, transporters and other related parameters, and present our own microarray data on messenger RNA expression for various transporters in the kidney cortex of M and F rats. With these data we would like to emphasize the importance of sex hormones in regulation of a variety of renal transport functions and to initiate further studies of gender-related differences in kidney structure and functions, which would enable us to better understand occurrence and development of various renal diseases, pharmacotherapy, and drug-induced nephrotoxicity in humans and animals.

Keywords

Androgens Estrogens Drug transporters Organic anion transporters Organic cation transporters Renal transporters Sex differences Sexual dimorphism 

Notes

Acknowledgments

This work was supported by grant no. 0022-0222148-2146 (Mammalian Renal Transporters; Gender Differences and Effects of Toxic Metals) from the Ministry of Science, Education and Sports, Republic of Croatia (I.S.). We would like to thank Isabelle Keller, Christian Fuhrimann, and Edgar Baer (Novartis Pharma AG, CH-4057 Basel, Switzerland) for excellent technical assistance in performing microarray experiments.

References

  1. 1.
    Ahlenstiel T, Burkhardt G, Kohler H, Kuhlmann MK (2006) Improved cold preservation of kidney tubular cells by means of adding bioflavonoids to organ preservation solutions. Transplantation 81:231–239PubMedGoogle Scholar
  2. 2.
    Alnouti Y, Petrick JS, Klaassen (2006) Tissue distribution and ontogeny of organic cation transporters in mice. Drug Metab Dispos 34:477–482PubMedGoogle Scholar
  3. 3.
    Alper SL, Natale J, Gluck S, Lodish HF, Brown D (1989) Subtypes of intercalated cells in rat kidney collecting duct defined by antibodies against erythroid band 3 and renal vacuolar H+-ATPase. Proc Natl Acad Sci USA 86:5429–5433PubMedGoogle Scholar
  4. 4.
    Alt JM, Maess B, Hackbarth H (1985) Species and strain differences in urinary protein excretion. Renal Physiol 8:301–309PubMedGoogle Scholar
  5. 5.
    Anakk S, Ku CY, Vore M, Strobel HW (2003) Insights into gender bias: rat cytochrome P450 3A9. J Pharmacol Exp Ther 305:703–709PubMedGoogle Scholar
  6. 6.
    Anton FM, Puig JG, Ramos T, Gonzales P, Ordas J (1986) Sex differences in uric acid metabolism in adults: evidence for a lack of influence of estradiol-17 beta (E2) on the renal handling of urate. Metabolism 35:343–348PubMedGoogle Scholar
  7. 7.
    Anzai N, Enomoto A, Endou H (2005) Renal urate handling: clinical relevance of recent advances. Curr Rheumatol Rep 7:227–234PubMedGoogle Scholar
  8. 8.
    Anzai N, Jutabha P, Kanai Y, Endou H (2005) Integrated physiology of proximal tubular organic anion transport. Curr Opin Nephrol Hypertens 14:472–479PubMedGoogle Scholar
  9. 9.
    Anzai N, Kanai Y, Endou H (2006) Organic anion transporter family: current knowledge. J Pharmacol Sci 100:411–426PubMedGoogle Scholar
  10. 10.
    Asaka J, Terada T, Okuda M, Katsura T, Inui K (2006) Androgen receptor is responsible for rat organic cation transporter 2 gene regulation but not for rOCT1 and rOCT3. Pharm Res 23:697–704PubMedGoogle Scholar
  11. 11.
    Babu E, Takeda M, Narikawa S, Kobayashi Y, Enomoto A, Tojo A, Cha SH, Sekine T, Sakthisekaran D, Endou H (2002) Role of human organic anion transporter 4 in the transport of ochratoxin A. Biochim Biophys Acta 1590:64–75PubMedGoogle Scholar
  12. 12.
    Bardin CW, Brown TR, Mills NC, Gupta C, Bullock LP (1978) The regulation of the β-glucuronidase gene by androgens and progestins. Biol Reprod 18:74–83PubMedGoogle Scholar
  13. 13.
    Beers KW, Thompson MA, Chini EN, Dousa TP (1996) Beta-estradiol inhibits Na+-Pi cotransport across renal brush border membranes from ovariectomized rats. Biochim Biophys Res Commun 221:442–445Google Scholar
  14. 14.
    Berg UB (2006) Differences in decline in GFR with age between males and females. Reference data on clearances of inulin and PAH in potential kidney donors. Nephrol Dial Transplant 21:2577–2582PubMedGoogle Scholar
  15. 15.
    Bergendi L, Benes L, Durackova Z, Ferencik M (1999) Chemistry, physiology and pathology of free radicals. Life Sci 65:1865–1874PubMedGoogle Scholar
  16. 16.
    Bergwerk AJ, Shi X, Ford AC, Kanai N, Jacquemin E, Burk RD, Bai S, Novikoff PM, Stieger B, Meier PJ, Schuster VL, Wokloff AW (1996) Immunological distribution of an organic anion transport protein in rat liver and kidney. Am J Physiol Gastrointest Liver Physiol 271:G231–G238Google Scholar
  17. 17.
    Berndt WO (1998) The role of transport in chemical nephrotoxicity. Toxicol Pathol 26:52–57PubMedGoogle Scholar
  18. 18.
    Bhat HK, Hacker HJ, Bannasch P, Thompson EA, Liehr JG (1993) Localization of estrogen receptors in interstitial cells of hamster kidney and in estradiol-induced renal tumors as evidence of the mesenchymal origin of this neoplasm. Cancer Res 53:5447–5451PubMedGoogle Scholar
  19. 19.
    Biemesderfer D, Reilly RF, Exner M, Igarashi P, Aronson PS (1992) Immunocytochemical characterization of Na+/H+ exchanger isoform NHE-1 in rabbit kidney. Am J Physiol 263:F833–F840PubMedGoogle Scholar
  20. 20.
    Birner G, Werner M, Ott MM, Dekant W (1995) Sex differences in hexachlorobutadiene biotransformation and nephrotoxicity. Toxicol Appl Pharmacol 132:203–212PubMedGoogle Scholar
  21. 21.
    Björnström L, Sjöberg M (2005) Mechanisms of estrogen receptor signaling: convergence of genomic and nongenomic actions on target genes. Mol Endocrinol 19:833–842PubMedGoogle Scholar
  22. 22.
    Blantz RC, Peterson OW, Blantz ER, Wilson CB (1988) Sexual differences in glomerular ultrafiltration: effect of androgen administration in ovariectomized rats. Endocrinology 122:767–773PubMedGoogle Scholar
  23. 23.
    Blazka ME, Nolan CV, Shaikh ZA (1988) Developmental and sex differences in cadmium distribution and metallothionein induction and localization. J Appl Toxicol 8:217–222PubMedGoogle Scholar
  24. 24.
    Blazka ME, Shaikh ZA (1991) Sex differences in hepatic and renal cadmium accumulation and metallothionein induction; role of estradiol. Biochem Pharmacol 41:775–780PubMedGoogle Scholar
  25. 25.
    Bobby B, Sitar DS (2001) The effect of lactate on sex differences in rat renal tubular energy-dependent transport of the organic cation amantadine. Pharmacology 62:188–192PubMedGoogle Scholar
  26. 26.
    Boorman GA, McDonald MR, Imoto S, Persing R (1992) Renal lesions induced by ochratoxin A exposure in the F344 rat. Toxicol Pathol 20:236–245PubMedGoogle Scholar
  27. 27.
    Boulkroun S, Moellic CL, Blot-Shabaud M, Farman N, Courtois-Coutry N (2005) Expression of androgen receptor and androgen regulation of NDRG2 in the rat collecting duct. Pfluegers Arch Eur J Physiol 451:388–394Google Scholar
  28. 28.
    Bowman HM, Hook JB (1972) Sex differences in organic ion transport by rat kidney. Proc Soc Exp Biol Med 141:258–262PubMedGoogle Scholar
  29. 29.
    Brandoni A, Villar SR, Torres AM (2004) Gender-related differences in the pharmacodynamics of furosemide in rats. Pharmacology 70:107–112PubMedGoogle Scholar
  30. 30.
    Bräunlich H, Meinig T, Grosch U (1993) Postnatal development of sex differences in renal tubular transport of p-aminohippurate (PAH) in rats. Exp Toxicol Pathol 45:309–313PubMedGoogle Scholar
  31. 31.
    Bridges CC, Zalups RK (2005) Molecular and ionic mimicry and the transport of toxic metals. Toxicol Appl Pharmacol 204:274–308PubMedGoogle Scholar
  32. 32.
    Budach W, Neuschäfer D, Wanke C, Chibout SD (2003) Generation of transducers for fluorescence-based microarrays with enhanced sensitivity and their application for gene expression profiling. Anal Chem 75:2571–2577PubMedGoogle Scholar
  33. 33.
    Buist SCN, Cherrington NJ, Choudhuri S, Hartley DP, Klaassen CD (2002) Gender-specific and developmental influences on the expression of rat organic anion transporters. J Pharmacol Exp Ther 301:145–151PubMedGoogle Scholar
  34. 34.
    Buist SCN, Cherrington NJ, Klaassen CD (2003) Endocrine regulation of rat organic anion transporters. Drug Metab Dispos 31:559–564PubMedGoogle Scholar
  35. 35.
    Buist SCN, Klaassen CD (2004) Rat and mouse differences in gender-predominant expression od organic anion transporter (OAT1–3; SLC22A6-8) mRNA levels. Drug Metab Dispos 32:620–625PubMedGoogle Scholar
  36. 36.
    Bumke-Vogt C, Bähr V, Diederich S, Herrmann SM, Anagnostopoulos I, Oelkers W, Quinkler M (2002) Expression of the progesterone receptor and progesterone-metabolising enzymes in the female and male human kidney. J Endocrinol 175:349–364Google Scholar
  37. 37.
    Burckhardt BC, Burckhardt G (2003) Transport of organic anions across the basolateral membrane of proximal tubule cells. Rev Physiol Biochem Pharmacol 146:95–158PubMedGoogle Scholar
  38. 38.
    Burckhardt G, Bahn A, Wolff N (2001) Molecular physiology of renal p-aminohippurate secretion. News Physiol Sci 16:114–118PubMedGoogle Scholar
  39. 39.
    Burckhardt G, Rizwan AN (2007) Organic anion transporters of the SLC22 family: biopharmaceutical, physiological, and pathological roles. Pharmacol Res 24:450–470Google Scholar
  40. 40.
    Burckhardt G, Wolff NA (2000) Structure of renal organic anion and cation transporters. Am J Physiol Renal Physiol 278:F853–F866PubMedGoogle Scholar
  41. 41.
    Carter AL, Stratman FW (1982) Sex steroid regulation of urinary excretion of carnitine in rats. J Steroid Biochem 17:211–216PubMedGoogle Scholar
  42. 42.
    Cerrutti JA, Brandoni A, Quaglia NB, Torres AM (2002) Sex differences in p-aminohippuric acid transport in rat kidney: role of membrane fluidity and expression of OAT1. Mol Cell Biochem 233:175–179PubMedGoogle Scholar
  43. 43.
    Cerrutti JA, Quaglia NB, Brandoni A, Torres AM (2002) Effect of gender on the pharmacokinetics of drugs secreted by the renal organic anions transport systems in the rat. Pharmacol Res 45:107–112PubMedGoogle Scholar
  44. 44.
    Cerrutti JA, Quaglia NB, Torres AM (2001) Characterization of the mechanisms involved in the gender differences in p-aminohippurate renal elimination in rats. Can J Physiol Pharmacol 79:805–813PubMedGoogle Scholar
  45. 45.
    Chambrey R, Warnock DG, Podevin RA, Bruneval P, Mandet C, Belair MF, Bariety J, Paillard M (1998) Immunolocalization of the Na+/H+ exchanger isoform NHE2 in rat kidney. Am J Physiol Renal Physiol 275:F379–F386Google Scholar
  46. 46.
    Chen C, Klaassen CD (2004) Rat multidrug resistance protein 4 (Mrp4, Abcc4): molecular cloning, organ distribution, postnatal renal expression, and chemical inducibility. Biochem Biophys Res Commun 317:46–53PubMedGoogle Scholar
  47. 47.
    Cheng X, Maher J, Lu H, Klaassen CD (2006) Endocrine regulation of gender-divergent organic anion transporting polypeptide (Oatp) expression. Mol Pharmacol 70:1291–1297PubMedGoogle Scholar
  48. 48.
    Cooper AE, Gray AJ, Collington J, Seddon H, Beattie I, Logan CJ (1996) Excretion and metabolism of tipredane, a novel glucocorticoid, in the rat, mouse, monkey, and human. Drug Metab Dispos 24:1071–1080PubMedGoogle Scholar
  49. 49.
    Couchourel D, Leclerc M, Filep J, Brunette MLG (2004) Testosterone enhances calcium reabsorption by the kidney. Mol Cell Endocrinol 222:71–81PubMedGoogle Scholar
  50. 50.
    Couse JF, Lindzey J, Grandien K, Gustafsson JA, Korach KS (1997) Tissue distribution and quantitative analysis of estrogen receptor-α (ERα) and estrogen receptor-β (ERβ) messenger ribonucleic acid in the wild-type and ERα-knockout mouse. Endocrinology 138:4613–4621PubMedGoogle Scholar
  51. 51.
    Cowley BD, Rupp JC, Muessel MJ, Gattone VH (1997) Gender and the effect of gonadal hormones on the progression of inherited polycystic kidney disease in rats. Am J Kidney Dis 29:265–272PubMedGoogle Scholar
  52. 52.
    Criddle RA, Zheng MH, Dick IM, Callus B, Prince RL (1997) Estrogen responsiveness of renal calbindin-D-28k gene expression in rat kidney. J Cell Biochem 65:340–348PubMedGoogle Scholar
  53. 53.
    Crofton JT, Dustan H, Share L, Brooks DP (1986) Vasopressin secretion in normotensive black and white men and women on normal and low sodium diets. J Endocrinol 108:191–199PubMedGoogle Scholar
  54. 54.
    Dantzler WH (2003) Regulation of renal proximal and distal tubule transport: sodium, chloride and organic anions. Comp Biochem Physiol A 136:453–478Google Scholar
  55. 55.
    Davidoff M, Caffier H, Schiebler TH (1980) Steroid hormone binding receptors in the rat kidney. Histochemistry 69:39–48PubMedGoogle Scholar
  56. 56.
    Deguchi J, Miyamoto M, Okada S (1995) Sex hormone-dependent renal cell carcinogenesis induced by ferric nitriloacetate in Wistar rats. Jpn J Cancer Res 86:1068–1071PubMedGoogle Scholar
  57. 57.
    De Mayo FJ, Zhao B, Takamoto N, Tsai SY (2002) Mechanisms of action of estrogen and progesterone. Ann NY Acad Sci 955:48–59Google Scholar
  58. 58.
    Dembic Z, Sabolic I (1982) Alcohol dehydrogenase activity in rat kidney cortex ctimulated by oestradiol. Biochim Biophys Acta 714:331–336PubMedGoogle Scholar
  59. 59.
    Dick IA, Liu J, Glendenning P, Prince RL (2003) Estrogen and androgen regulation of plasma membrane calcium pump activity in immortalized distal tubule kidney cells. Mol Cell Endocrinol 212:11–18PubMedGoogle Scholar
  60. 60.
    Distefano A, Roinel N, Derouffignac C, Wittner M (1993) Transepithelial Ca2+ and Mg2+ transport in the cortical thick ascending limb of Henles loop of the mouse is a voltage-dependent process. Renal Physiol Biochem 16:157–166Google Scholar
  61. 61.
    Dubey RK, Jackson EK (2001) Estrogen-induced cardiorenal protection: potential cellular, biochemical, and molecular mechanisms. Am J Physiol Renal Physiol 280:F365–F388PubMedGoogle Scholar
  62. 62.
    Echeverria OM, Maciel AG, Traish AM, Wotiz HH, Ubaldo E, Vasquez-Nin GH (1994): Immuno-electron microscopic localization of estradiol receptor in cells of male and female reproductive and non-reproductive organs. Biol Cell 81:257–265PubMedGoogle Scholar
  63. 63.
    Ekaratanawong S, Anzai N, Jatubha P, Miyazaki H, Noshiro R, Takeda M, Kanai Y, Sophasan S, Endou H (2004) Human organic anion transporter 4 is a renal apical organic anion/dicarboxylate exchanger in the proximal tubules. J Pharmacol Sci 94:297–304PubMedGoogle Scholar
  64. 64.
    Enmark E, Pelto-Huikko M, Grandien K, Lagercrantz S, Lagercrantz J, Fried G, Nordenskjold M, Gustafsson JA (1997) Human estrogen receptor β-gene structure, chromosomal localization, and expression pattern. J Clin Endocrinol Metab 82:4258–4265PubMedGoogle Scholar
  65. 65.
    Enomoto A, Takeda M, Shimoda M, Narikawa S, Kobayashi Y, Kobayashi Y, Yamamoto T, Sekine T, Cha SH, Niwa T, Endou H (2002) Interaction of human organic anion transporters 2 and 4 with organic anion transporter inhibitors. J Pharmacol Exp Ther 301:797–802PubMedGoogle Scholar
  66. 66.
    Eraly SA, Vallon V, Vaughan DA, Gangoiti JA, Richter K, Nagle M, Monte JC, Rieg T, Truong DM, Long JM, Barshop BA, Kaler G, Nigam SK (2006) Decreased renal organic anion secretion and plasma accumulation of endogenous organic anions in OAT1 knock-out mice. J Biol Chem 281:5072–5083PubMedGoogle Scholar
  67. 67.
    Erdely A, Greenfeld Z, Wagner L, Baylis C (2003) Sexual dimorphism in the aging kidney: effects on injury and nitric oxide system. Kidney Int 63:1021–1026PubMedGoogle Scholar
  68. 68.
    Fan J, Chandhoke PS, Grampsas SA (1999) Role of sex hormones in experimental calcium nephrolithiasis. J Am Soc Nephrol 10(Suppl 14):S376–S380PubMedGoogle Scholar
  69. 69.
    Fekete A, Vanney A, Ver A, Vasarhelyi B, Muller V, Ouyang N, Reusz G, Tullasay T, Szabo AJ (2004) Sex differences in the alterations of Na+,K+-ATPase following ischaemia-reperfusion injury in the rat kidney. J Physiol (Lond) 555:471–480Google Scholar
  70. 70.
    Felder MR, Watson G, Huff MO, Ceci JD (1988) Mechanism of induction of mouse kidney alcohol dehydrogenase by androgen. Androgen-induced stimulation of transcription of the Adh-1 gene. J Biol Chem 263:14531–14537PubMedGoogle Scholar
  71. 71.
    Franconi F, Brunelleschi S, Steardo L, Cuomo V (2007) Gender differences in drug responses. Pharmacol Res 55:81–95PubMedGoogle Scholar
  72. 72.
    Franson KL, Kuk JM, Lam NP, Lau AH (1996) Gender effect on diuretic response to hydrochlorothiazide and furosemide. Int J Clin Pharmacol Ther 34:101–105PubMedGoogle Scholar
  73. 73.
    Frattini A, Pangrazio A, Suzani L, Sobacchi C, Mirolo M, Abinun M, Andolina M, Flanagan A, Horwitz EM, Mihci E, Notarangelo LD, Ramenghi U, Teti A, Van Hove J, Vujic D, Young T, Albertini A, Orchard PJ, Vezzoni P, Villa A (2003) Chloride channel ClCN7 mutations are responsible for severe recessive, dominant, and intermediate osteopetrosis. J Bone Miner Res 18:1740–1747PubMedGoogle Scholar
  74. 74.
    Gandhi M, Aweeka F, Greenblatt RM, Blaschke TF (2004) Sex differences in pharmacokinetics and pharmacodynamics. Annu Rev Pharmacol Toxicol 44:499–523PubMedGoogle Scholar
  75. 75.
    Gobinet J, Poujol N, Sultan C (2002) Molecular action of androgens. Mol Cell Endocrinol 198:15–24PubMedGoogle Scholar
  76. 76.
    Gorboulev V, Ulzheimer JC, Akhoundova A, Ulzheimer-Teuber I, Karbach U, Quester S, Baumann C, Lang F, Busch AE, Koepsell H (1997) Cloning and characterization of two human polyspecific organic cation transporters. DNA Cell Biol 16:871–881PubMedGoogle Scholar
  77. 77.
    Gotoh Y, Kato Y, Stieger B, Meier PJ, Sugiyama Y (2002) Gender difference in the Oatp1-mediated tubular reabsorption of estradiol 17β-D-glucuronide in rats. Am J Physiol Endocrinol Metab 282:E1245–E1254PubMedGoogle Scholar
  78. 78.
    Groenestege WMT, Hoenderop JG, van den Heuvel L, Knoers N, Bindels RJ (2006) The epithelial Mg2+ channel transient receptor potential melastatin 6 is regulated by dietary Mg2+ content and estrogens. J Am Soc Nephrol 17:1035–1043PubMedGoogle Scholar
  79. 79.
    Groves CE, Suhre WB, Cherrington NJ, Wright SH (2006) Sex differences in the mRNA, protein, and functional expression of organic anion transporter (Oat) 1, Oat3, and organic cation transporter (Oct) 2 in rabbit renal proximal tubules. J Pharmacol Exp Ther 316:743–752PubMedGoogle Scholar
  80. 80.
    Hadzic A, Mackovic-Basic M, Sabolic I (1988) Stimulation of alkaline phosphatase activity by estradiol in rat renal cortical brush-border membranes. Period Biol 90:341–348Google Scholar
  81. 81.
    Hall JM, Couse JF, Korach KS (2001) The multifaceted mechanisms of estradiol and estrogen receptor signaling. J Biol Chem 276:36869–36872PubMedGoogle Scholar
  82. 82.
    Han HJ, Jung JC, Taub M (1999) Response of primary rabbit kidney proximal tubule cells to estrogens. J Cell Physiol 178:35–43PubMedGoogle Scholar
  83. 83.
    Han HJ, Lee YH, Park KM, Taub M (2002) Estradiol-17β stimulates phosphate uptake and is mitogenic for primary rabbit renal proximal tubule cells. Exp Nephrol 10:355–364PubMedGoogle Scholar
  84. 84.
    Harada K, Inoue K, Morikawa A, Yoshinaga T, Saito N, Koizumi A (2005) Renal clearance of perfluorooctane sulfonate and perfluorooctanoate in humans and their species-specific excretion. Environ Res 99:253–261PubMedGoogle Scholar
  85. 85.
    Hediger MA (Guest Editor) (2004) The ABCs of solute carriers: physiological, pathological, and therapeutic implications of human membrane transport proteins. Pflügers Arch Eur J Physiol 447:5Google Scholar
  86. 86.
    Heinlein CA, Chang CS (2002) The roles of androgen receptors and androgen-binding proteins in nongenomic androgen actions. Mol Endocrinol 16:2181–2187PubMedGoogle Scholar
  87. 87.
    Henderson CJ, Wolf CR (1991) Evidence that the androgen receptor mediates sexual differentiation of mouse renal P-450 expression. Biochem J 278:499–503PubMedGoogle Scholar
  88. 88.
    Ho PC, Triggs EJ, Bourne DW, Heazlewood VJ (1985) The effects of age and sex on the disposition of acetylsalicylic acid and its metabolites. Br J Clin Pharmacol 19:675–684PubMedGoogle Scholar
  89. 89.
    Ho RH, Kim RB (2005) Transporters and drug therapy: Implications for drug disposition and disease. Clin Pharmacol Ther 78:260–277PubMedGoogle Scholar
  90. 90.
    Hosoyamada M, Ichida K, Enomoto A, Hosoya T, Endou H (2004) Function and localization of urate transporter 1 in mouse kidney. J Am Soc Nephrol 15:261–268PubMedGoogle Scholar
  91. 91.
    Hu ZL, Bonifas JM, Beech J, Bench G, Shigihara T, Ogawa H, Ikeda S, Mauro T, Epstein EH (2000) Mutations in ATP2C1, encoding a calcium pump, cause Hailey-Hailey disease. Nat Genet 24:61–65PubMedGoogle Scholar
  92. 92.
    Huang KC, McIntosh BJ (1955) Effect of sex hormones on renal transport of p-aminohippuric acid. Am J Physiol 183:387–390PubMedGoogle Scholar
  93. 93.
    Hübner CA, Jentsch TJ (2002) Ion channel diseases. Hum Mol Genet 11:2435–24445PubMedGoogle Scholar
  94. 94.
    Iba MM, Fung J, Thomas PE, Park Y (1999) Constitutive and induced expression by pyridine and beta-naphtoflavone of rat CYP1A is sexually dimorphic. Arch Toxicol 73:208–216PubMedGoogle Scholar
  95. 95.
    Iguchi M, Takamura C, Umekawa T, Kurita T, Kohri K (1999) Inhibitory effects of female sex hormones on urinary stone formation in rats. Kidney Int 56:479–485PubMedGoogle Scholar
  96. 96.
    Inui KI, Masuda S, Saito H (2000) Cellular and molecular aspects of drug transport in the kidney. Kidney Int 58:944–958PubMedGoogle Scholar
  97. 97.
    Isern J, Hagenguch B, Stieger B, Meier PJ, Meseguer A (2001) Functional analysis and androgen-regulated expression of mouse organic anion transporting polypeptide 1 (Oatp1) in the kidney. Biochim Biophys Acta 1518:73–78PubMedGoogle Scholar
  98. 98.
    Izzat NN, Rosborough JP (1989) Renal function in conscious dogs: potential effect of gender on measurements. Res Exp Med (Berl) 189:371–379Google Scholar
  99. 99.
    Janssen FM, Young EM, Ruelius HW (1976) Effect of sex hormones on the disposition in rats of 1-aminocyclohexane carboxylic acid, a metabolite of semisynthetic penicillin. Drug Metab Dispos 4:540–546PubMedGoogle Scholar
  100. 100.
    Jean-Faucher C, Berger M, Gallon C, Turckheim M, Veyssiere G, Jean C (1987) Sex-related differences in renal size in mice: ontogeny and influence of neonatal androgens. J Endocrinol 115:241–246PubMedGoogle Scholar
  101. 101.
    Jelinsky SA, Harris HA, Brown EL, Flanagan K, Zhang X, Tunkey C, Lai K, Lane MV, Simcoe DK, Evans MJ (2003) Global transcription profiling of estrogen activity: estrogen receptor α regulates gene expression in the kidney. Endocrinology 144:701–710PubMedGoogle Scholar
  102. 102.
    Ji H, Pesce C, Zheng W, Kim J, Zhang Y, Menini S, Haywood JR, Sandberg K (2005) Sex differences in renal injury and nitric oxide production in renal wrap hypertension. Am J Physiol Heart Circ Physiol 288:H43–H47PubMedGoogle Scholar
  103. 103.
    Kahraman A, Erkasap N, Serteser M, Koken T (2003) Protective effect of quercetin on renal ischemia/reperfusion injury in rats. J Nephrol 16:219–224PubMedGoogle Scholar
  104. 104.
    Kalsotra A, Anakk S, Boehme CL, Strobel HW (2002) Sexual dimorphism and tissue specificity in the expression of CYP4F forms in Sprague Dawley rats. Drug Metab Dispos 30:1022–1028PubMedGoogle Scholar
  105. 105.
    Karbach U, Kricke J, Meyer-Wentrup F, Gorboulev V, Volk C, Loffing-Cueni D, Kaissling B, Bachmann S, Koepsell H (2000) Localization of organic cation transporters OCT1 and OCT2 in rat kidney. Am J Physiol Renal Physiol 279:F679–F687PubMedGoogle Scholar
  106. 106.
    Karniski LP, Lotcher M, Fucentese M, Hilfiker H, Biber J, Murer H (1998) Immunolocalization of sat-1 sulfate/oxalate/bicarbonate anion exchanger in the rat kidney. Am J Physiol Renal Physiol 275:F79–F87Google Scholar
  107. 107.
    Kato Y, Kuge K, Kusuhara H, Meier PJ, Sugiyama Y (2002) Gender difference in the urinary excretion of organic anions in rats. J Pharmacol Exp Ther 302:483–489PubMedGoogle Scholar
  108. 108.
    Kausalya PJ, Amasheh S, Gunzel D, Wurps H, Muller D, Fromm M, Hunziker W (2006) Disease-associated mutations affect intracellular traffic and paracellular Mg2+ transport function of Claudin-16. J Clin Invest 116:878–891PubMedGoogle Scholar
  109. 109.
    Kerb R (2006) Implications of genetic polymorphism in drug transporters for pharmacotherapy. Cancer Lett 234:4–33PubMedGoogle Scholar
  110. 110.
    Kher A, Meldrum KK, Wang MJ, Tsai BM, Pitcher JA, Meldrum DR (2005) Cellular and molecular mechanisms of sex differences in renal ischemia-reperfusion injury. Cardiovasc Res 67:594–603PubMedGoogle Scholar
  111. 111.
    Kimura N, Mizokami A, Oonuma T, Sasano H, Nagura H (1993) Immunocytochemical localization of androgen receptor with polyclonal antibody in paraffin-embedded human tissues. J Histochem Cytochem 41:671–678PubMedGoogle Scholar
  112. 112.
    Kiuchi-Saishin Y, Gotoh S, Furuse M, Takasuga A, Tano Y, Tsukita S (2002) Differential expression patterns of claudins, tight junction membrane proteins, in mouse nephron segments. J Am Soc Nephrol 13:875–886PubMedGoogle Scholar
  113. 113.
    Kleinman LI, Loewenstein MS, Goldstein L (1966) Sex difference in the transport of p-aminohippurate by the rat kidney. Endocrinology 78:403–406PubMedCrossRefGoogle Scholar
  114. 114.
    Kobayashi K, Uchida S, Mizutani S, Sasaki S, Marumo F (2001) Intrarenal and cellular localization of CLC-K2 protein in the mouse kidney. J Am Soc Nephrol 12:1327–1334PubMedGoogle Scholar
  115. 115.
    Kobayashi Y, Hirokawa N, Ohshiro N, Sekine T, Sasaki T, Tokuyama S, Endou H, Yamamoto T (2002) Differential gene expression of organic anion transporters in male and female rats. Biochem Biophys Res Commun 290:482–487PubMedGoogle Scholar
  116. 116.
    Kobayashi Y, Ohbayashi M, Kohyama N, Yamamoto T (2005) Mouse organic anion transporter 2 and 3 (mOAT2/3 (Slc22a7/8)) mediates the renal transport of bumetanide. Eur J Pharmacol 524:44–48PubMedGoogle Scholar
  117. 117.
    Kobayashi Y, Ohshiro N, Shibusawa A, Sasaki T, Tokuyama S, Sekine T, Endou H, Yamamoto T (2002) Isolation, characterization and differential gene expression of multispecific organic anion transporter 2 in mice. Mol Pharmacol 62:7–14PubMedGoogle Scholar
  118. 118.
    Koepsell H (2004) Polyspecific organic cation transporters: their functions and interactions with drugs. Trends Pharmacol Sci 25:375–381PubMedGoogle Scholar
  119. 119.
    Koepsell H, Gorboulev V, Arndt P (1999) Molecular pharmacology of organic cation transporters in kidney. J Membr Biol 167:103–117PubMedGoogle Scholar
  120. 120.
    Koizumi T (1995) Deoxyribonuclease-II (DNAse-II) activity in mouse tissues and body fluids. Jikken Dobutsu 44:169–171Google Scholar
  121. 121.
    Koizumi T (1995) Tissue distribution of deoxyribonuclease I (DNASE I) activity level in mice and its sexual dimorphism. Jikken Dobutsu 44:181–185Google Scholar
  122. 122.
    Kudo N, Katakura M, Sato Y, Kawashima Y (2002) Sex hormone-regulated renal transport of perfluorooctanoic acid. Chem-Biol Interact 139:301–316PubMedGoogle Scholar
  123. 123.
    Kuiper GGJM, Carlsson B, Grandien K, Enmark E, Haggblad J, Nilsson S, Gustafsson JA (1997) Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors α and β. Endocrinology 138:863–870PubMedGoogle Scholar
  124. 124.
    Kuo SM, MacLean ME, McCormick K, Wilson JX (2004) Gender and sodium-ascorbate transporter isoforms determine ascorbate concentrations in mice. J Nutr 134:2216–2221PubMedGoogle Scholar
  125. 125.
    Lane PH, Snelling DM, Babushkina-Patz N, Langer WJ (2001) Sex differences in the renal transforming growth factor-beta 1 system after puberty. Pediatr Nephrol 16:61–68PubMedGoogle Scholar
  126. 126.
    Launay-Vacher V, Izzedine H, Karie S, Hulot JS, Baumelou A, Deray G (2006) Renal tubular drug transporters. Nephron Physiol 103:p97–p106PubMedGoogle Scholar
  127. 127.
    Lee HJ, Chang C (2003) Recent advances in androgen receptor action. Cell Mol Life Sci 60:1613–1622PubMedGoogle Scholar
  128. 128.
    Lee W, Kim RB (2004) Transporters and renal drug elimination. Annu Rev Pharmacol Toxicol 44:137–166PubMedGoogle Scholar
  129. 129.
    Levillain O, Diaz JJ, Blanchard O, Dechaud H (2005) Testosterone down-regulates ornithine aminotransferase gene and up-regulates arginase II and ornithine decarboxylase genes for polyamines synthesis in the murine kidney. Endocrinology 146:950–959PubMedGoogle Scholar
  130. 130.
    Levillain O, Greco A, Diaz JJ, Augier R, Didier A, Kindbeiter K, Catez F, Cayre M (2003) Influence of testosterone on regulation of ODC, antizyme, and N1-SSAT gene expression in mouse kidney. Am J Physiol Renal Physiol 285:F498–F506PubMedGoogle Scholar
  131. 131.
    Levin ER (2001) Cell localization, physiology, and nongenomic actions of estrogen receptors. J Appl Physiol 91:1860–1867PubMedGoogle Scholar
  132. 132.
    Li M, Anderson GD, Wang J (2006) Drug–drug interactions involving membrane transporters in the human kidney. Expert Opin Drug Metab Toxicol 2:505–532PubMedGoogle Scholar
  133. 133.
    Li T, Walsh JR, Ghishan FK, Bai L (2004) Molecular cloning and characterization of a human urate transporter (hURAT1) gene promoter. Biochim Biophys Acta 1681:53–58PubMedGoogle Scholar
  134. 134.
    Ljubojevic M, Balen D, Breljak D, Kusan M, Anzai N, Bahn A, Burckhardt G, Sabolic I (2007) Renal expression of organic anion transporter OAT2 in rats and mice is regulated by sex hormones. Am J Physiol Renal Physiol 292:F361–F372PubMedGoogle Scholar
  135. 135.
    Ljubojevic M, Herak-Kramberger CM, Hagos Y, Bahn A, Endou H, Burckhardt G, Sabolic I (2004) Rat renal cortical OAT1 and OAT3 exhibit gender differences determined by both androgen stimulation and estrogen inhibition. Am J Physiol Renal Physiol 287:F124–F138PubMedGoogle Scholar
  136. 136.
    Lock EA, Reed CJ (1998) Xenobiotic metabolizing enzymes of the kidney. Toxicol Pathol 26:18–25PubMedCrossRefGoogle Scholar
  137. 137.
    Lohr JW, Willsky GR, Acara MA (1998) Renal drug metabolism. Pharmacol Rev 50:107–141PubMedGoogle Scholar
  138. 138.
    Lu H, Lei X, Klaassen C (2006) Gender differences in renal nuclear receptors and aryl hydrocarbon receptor in 5/6 nephrectomized rats. Kidney Int 70:1920–1928PubMedGoogle Scholar
  139. 139.
    Lu R, Kanai N, Bao Y, Wolkoff AW, Schuster VL (1996) Regulation of renal oatp mRNA expression by testosterone. Am J Physiol Renal Physiol 270:F332–F337Google Scholar
  140. 140.
    Ludwig M, Utsch B (2004) Dent disease-like phenotype and chloride channel ClC-4 (CLCN4) gene. Am J Med Genet, Part A 128A:434–435Google Scholar
  141. 141.
    Ma J, Graves J, Bradbury JA, Zhao Y, Swope DL, King L, Qu W, Clark J, Myers P, Walker V, Lindzey J, Korach KS, Zeldin DC (2004) Regulation of mouse renal CYP2J5 expression by sex hormones. Mol Pharmacol 65:730–743PubMedGoogle Scholar
  142. 142.
    Ma YX, Kawabata T, Hamazaki S, Ogino T, Okada S (1998) Sex differences in oxidative damage in DDY mouse kidney treated with a renal carcinogen, iron nitriloacetate. Carcinogenesis 19:1983–1988PubMedGoogle Scholar
  143. 143.
    MacKay LL, MacKay EM (1927) Factors which determine renal weight; III. Sex. Am J Physiol 83:196–201Google Scholar
  144. 144.
    Madeddu P, Emanueli C, Varoni MV, Demontis MP, Anania V, Gorioso N, Chao J (1997) Regulation of bradykinin B2-receptor expression by oestrogen. Br J Pharmacol 121:1763–1769PubMedGoogle Scholar
  145. 145.
    Maher JM, Slitt AL, Cherrington NJ, Cheng X, Klaassen CD (2005) Tissue distribution and hepatic and renal ontogeny of the multidrug resistance-associated protein (MRP) family in mice. Drug Metab Dispos 33:947–955PubMedGoogle Scholar
  146. 146.
    Markarevich BM, Gregory RR (1991) Preliminary characterization and partial purification of rat uterine nuclear type II binding sites. Biochem Biophys Res Commun 177:1283–1290Google Scholar
  147. 147.
    Markarevich BM, Roberts RR, Alejandro MA, Johnson GA, Middleditch BS, Clark JH (1988) Bioflavonoid interaction with rat uterine type II binding sites and cell growth inhibition. J Steroid Biochem 30:71–78Google Scholar
  148. 148.
    Martucci CP, Fishmann J (1993) P450 enzyme of estrogen metabolism. Pharmacol Ther 57:237–257PubMedGoogle Scholar
  149. 149.
    Masuda S, Ibaramoto K, Takeuchi A, Saito H, Hashimoto Y, Inui KI (1999) Cloning and functional characterization of a new multispecific organic anion transporter, OAT-K2, in rat kidney. Mol Pharmacol 55:743–752PubMedGoogle Scholar
  150. 150.
    Meibohm B, Beierle I, Derendorf H (2002) How important are gender differences in pharamacokinetics? Clin Pharmacokinet 41:329–342PubMedGoogle Scholar
  151. 151.
    Melia MJ, Bofill N, Hubank M, Meseguer A (1998) Identification of androgen-regulated genes in mouse kidney by representational difference analysis and random arbitrarily primed polymerase chain reaction. Endocrinology 139:688–695PubMedGoogle Scholar
  152. 152.
    Metcalfe PD, Meldrum KK (2006) Sex differences and the role of sex steroids in renal injury. J Urol 176:15–21PubMedGoogle Scholar
  153. 153.
    Miles AT, Hawksworth GM, Beattie JH, Rodilla V (2000) Induction, regulation, degradation, and biological significance of mammalian metallothioneins. Crit Rev Biochem Mol Biol 35:35–70PubMedGoogle Scholar
  154. 154.
    Miller JA, Anacta LA, Cattran DC (1999) Impact of gender on the renal response to angiotensin II. Kidney Int 55:278–285PubMedGoogle Scholar
  155. 155.
    Moestrup SK, Verroust PJ (2001) Megalin and cubilin-mediated endocytosis of protein-bound vitamins, lipids, and hormones in polarized epithelia. Annu Rev Nutrit 21:407–428Google Scholar
  156. 156.
    Moriarty K, Kim KH, Bender JR (2006) Estrogen receptor-mediated rapid signaling. Endocrinology 147:5557–5563PubMedGoogle Scholar
  157. 157.
    Morris ME, Lee HJ, Predko LM (2003) Gender differences in the membrane transport of endogenous and exogenous compounds. Pharmacol Rev 55:229–240PubMedGoogle Scholar
  158. 158.
    Mount DB, Baekgaard A, Hall AE, Plata C, Xy J, Beier DR, Gamba G, Hebert SC (1999) Isoforms of the Na-K-2Cl cotransporter in murine TAL I. Molecular characterization and intrarenal localization. Am J Physiol Renal Physiol 276:F347–F358Google Scholar
  159. 159.
    Motohashi H, Sakurai Y, Saito H, Masuda S, Urakami Y, Goto M, Fukatsu A, Ogawa O, Inui KI (2002) Gene expression levels and immunolocalization of organic ion transporters in the human kidney. J Am Soc Nephrol 13:866–874PubMedGoogle Scholar
  160. 160.
    Mulroney SE, Woda C, Johnson M, Pesce C (1999) Gender differences in renal growth and function after uninephrectomy in adult rats. Kidney Int 56:944–953PubMedGoogle Scholar
  161. 161.
    Munger K, Baylis CB (1988) Sex differences in renal hemodynamics in rats. Am J Physiol Renal Physiol 254:F223–F231Google Scholar
  162. 162.
    Nagao S, Kusaka M, Nishii K, Marunouchi T, Kurahashi H, Takahashi H, Grantham J (2005) Androgen receptor pathway in rats with autosomal dominant polycystic disease. J Am Soc Nephrol 16:2052–2062PubMedGoogle Scholar
  163. 163.
    Nakamura S, Sugawara Y, Fukushima T, Ito Y, Ohashi M, Takaiti O (1993) Disposition and metabolic fate of clentiazem in rats and dogs. Biol Pharm Bull 16:647–655PubMedGoogle Scholar
  164. 164.
    Nascimento DS, Reis CU, Goldenberg RC, Ortiga-Carvalho TM, Pazos-Moura CC, Guggino SE, Guggino WB, Morales MM (2003) Estrogen modulates ClC-2 chloride channel gene expression in rat kidney. Pfluegers Arch Eur J Physiol 446:593–599Google Scholar
  165. 165.
    Neal GE, Judah DJ, Hard GG, Ito N (2003) Differences in ethoxyquin nephrotoxicity between male and female F344 rats. Food Chem Toxicol 41:193–200PubMedGoogle Scholar
  166. 166.
    Neugarten J (2002) Gender and the progression of renal disease. J Am Soc Nephrol 13:2807–2809PubMedGoogle Scholar
  167. 167.
    Neugarten J, Acharia A, Silbiger SR (2000) Effect of gender on the progression of nondiabetic renal disease. J Am Soc Nephrol 11:319–329PubMedGoogle Scholar
  168. 168.
    Neugarten J, Ding Q, Friedman A, Lei J, Silbiger S (1997) Sex hormones and renal nitric oxide synthases. J Am Soc Nephrol 8:1240–1246PubMedGoogle Scholar
  169. 169.
    Neugarten J, Kasiske B, Silbiger SR, Nyengaard JR (2002) Effects of sex on renal structure. Nephron 90:139–144PubMedGoogle Scholar
  170. 170.
    Neuschäfer D, Budach W, Wanke C, Chibout SD (2003) Evanescent resonator chips: a universal platform with superior sensitivity for fluorescence-based microarrays. Biosens Bioelectron 18:489–497PubMedGoogle Scholar
  171. 171.
    Nielsen S, Frokiaer J, Marples D, Known TH, Agre P, Knepper MA (2002) Aquaporins in the kidney: from molecules to medicine. Physiol Rev 82:205–244PubMedGoogle Scholar
  172. 172.
    Nilsson S, Mäkelä, Treuter E, Tujague M, Thomsen J, Andersson G, Enmark E, Petterson K, Warner M, Gustafsson JA (2001) Mechanisms of estrogen action. Physiol Rev 81:1535–1565PubMedGoogle Scholar
  173. 173.
    Odeberg JM, Callreus T, Lundin S, Roth EB, Hoglund P (2004) A pharmacokinetic and pharmacodynamic study of desmopressin: evaluating sex differences and the effect of pre-treatment with piroxicam, and further validation of an indirect response model. J Pharm Pharmacol 56:1389–1398PubMedGoogle Scholar
  174. 174.
    Ohno S, Stenius C, Christian L, Harris C, Ivey C (1970) More about the testosterone induction of kidney alcohol dehydrogenase activity in the mouse. Biochem Genet 4:565–577Google Scholar
  175. 175.
    O’Loughlin PD, Morris HA (2003) Oophorectomy acutely increases calcium excretion in adult rats. J Nutr 133:2277–2280PubMedGoogle Scholar
  176. 176.
    Ouar Z, Sole E, Bens M, Rafestin-Oblin ME, Meseguer A, Vandewalle A (1998) Pleiotropic effects of dihydrotestosterone in immortalized mouse proximal tubule cells. Kidney Int 53:59–66PubMedGoogle Scholar
  177. 177.
    Oudar O, Elger M, Bankir L, Ganten D, Ganten U, Kriz W (1991) Differences in rat kidney morphology between males, females and testosterone-treated females. Renal Physiol Biochem 14:92–102PubMedGoogle Scholar
  178. 178.
    Overholser BR, Kays MB, Forrest A, Sowinski KM (2004) Sex-related differences in the pharamacokinetics of oral ciprofloxacin. J Clin Pharamacol 44:1012–1022Google Scholar
  179. 179.
    Pamphlett R, Ewan KB, McQuilty, Waley P (1997) Gender differences in the uptake of inorganic mercury by motor neurons. Neurotoxicol Teratol 19:287–293PubMedGoogle Scholar
  180. 180.
    Pan J, Hong JY, Yang CS (1992) Post-transcriptional regulation of mouse renal cytochrome P450 2E1 by testosterone. Arch Biochem Biophys 299:110–115PubMedGoogle Scholar
  181. 181.
    Paunescu TG, Da Silva N, Marshansky V, McKee M, Breton S, Brown D (2004) Expression of the 56-kDa B2 subunit isoform of the vacuolar H+-ATPase in proton-secreting cells of the kidney and epididymis. Am J Physiol Cell Physiol 287:C149–C162PubMedGoogle Scholar
  182. 182.
    Perucca J, Bouby N, Valeix P, Bankir L (2007) Sex differences in urine concentration across differing ages, sodium intake and level of kidney disease. Am J Physiol Regul Integr Comp Physiol 292:R700–R705PubMedGoogle Scholar
  183. 183.
    Pettersson K, Gustafsson JA (2001) Role of estrogen receptor beta in estrogen action. Annu Rev Physiol. 63:165–192PubMedGoogle Scholar
  184. 184.
    Peysner K, Forsling ML (1990) Effect of ovariectomy and treatment with ovarian steroids on vasopressin release and fluid balance in the rat. J Endocrinol 124:277–284PubMedGoogle Scholar
  185. 185.
    Prieto I, Arechaga G, Segarra AB, Alba F, de Gasparo M, Ramirez M (2002) Effects of dehydration on renal aminopeptidase activities in adult male and female rats. Reg Pept 106:27–32Google Scholar
  186. 186.
    Quan A, Chakravarty S, Chen JK, Chen JC, Loleh S, Saini N, Harris RC, Capdevila J, Quigley R (2004) Androgens augment proximal tubule transport. Am J Physiol Renal Physiol 287:F452–F459PubMedGoogle Scholar
  187. 187.
    Quinkler M, Bujalska IJ, Kaur K, Onyimba CU, Buhner S, Alloilo B, Hughes SV, Hewison M, Stewart PM (2005) Androgen receptor-mediated regulation of the α-subunit of the epithelial sodium channel in human kidney. Hypertension 46:787–798PubMedGoogle Scholar
  188. 188.
    Quinkler M, Bumke-Vogt C, Meyer B, Bahr V, Oelkers W, Diederich S (2003) The human kidney is a progesterone-metabolizing and androgen-producing organ. J Clin Endocrinol Metab 88:2803–2809PubMedGoogle Scholar
  189. 189.
    Qulali M, Ross RA, Crabb DW (1991) Estradiol induces class I alcohol dehydrogenase activity and mRNA in kidney of female rats. Arch Biochem Biophys 288:406–413PubMedGoogle Scholar
  190. 190.
    Rankin GO, Beers KW, Teets VJ, Nicoll DW, Anestis DK, Brown PI, Wang RT (1994) Acute N-(3,5-dichlorophenyl) succinimide nephrotoxicity in female Fischer 344 rats. Toxicology 88:151–164PubMedGoogle Scholar
  191. 191.
    Rasonyi T, Schlatter J, Dietrich DR (1999) The role of alpha2 μ-globulin in ochratoxin A induced renal toxicity and tumors in F344 rats. Toxicol Lett 104:83–92PubMedGoogle Scholar
  192. 192.
    Reckelhoff JF, Hennington BS, Moore AG, Blanchard EJ, Cameron J (1998) Gender differences in the renal nitric oxide (NO) system: dissociation between expression and endothelial NO synthase and renal hemodynamic response to NO synthase inhibition. Am J Hypertens 11:97–104PubMedGoogle Scholar
  193. 193.
    Reckelhoff JF, Yanes LL, Iliescu R, Fortepiani LA, Granger JP (2005) Testosterone supplementation in aging men and women: possible impact on cardiovascular-renal disease. Am J Physiol Renal Physiol 289:F941–F948PubMedGoogle Scholar
  194. 194.
    Remuzzi A, Puntorieri S, Mazzoleni A, Remuzzi G (1988) Sex related differences in glomerular ultrafiltration and proteinuria in Munich-Wistar rats. Kidney Int 34:481–486PubMedGoogle Scholar
  195. 195.
    Reyes JL, Lamas M, Martin D, Namorado MD, Islas S, Luna J, Tauc M, Gonzales-Marisca L (2002) The renal segmental distribution of claudins changes with development. Kidney Int 62:476-487PubMedGoogle Scholar
  196. 196.
    Reyes JL, Melendez E, Alegria A, Jaramillo-Juarez F (1998) Influence of sex differences on the renal secretion of organic anions. Endocrinology 139:1581–1587PubMedGoogle Scholar
  197. 197.
    Rinn JL, Rozowsky JS, Laurenzi IJ, Petersen PH, Zou K, Zhong W, Gerstein M, Snyder M (2004) Major molecular differences between mammalian sexes are involved in drug metabolism and renal function. Dev Cell 6:791–800PubMedGoogle Scholar
  198. 198.
    Robertson EE, Rankin GO (2006) Human renal organic anion transporters: Characteristics and contributions to drug and drug metabolite excretion. Pharmacol Ther 109:399–412PubMedGoogle Scholar
  199. 199.
    Rogers JL, Mitchell AR, Maric C, Sandberg K, Myers A, Mulroney SE (2007) Effect of sex hormones on renal estrogen and angiotensin type 1 receptors in female and male rats. Am J Physiol Regul Integr Comp Physiol 292:R794–R799PubMedGoogle Scholar
  200. 200.
    Royaux IE, Wall SM, Karniski LP, Everett LA, Suzuki K, Knepper MA, Green ED (2001) Pendrin, encoded by the Pendred syndrome gene, resides in the apical region of renal intercalated cells and mediates bicarbonate secretion. Proc Natl Acad Sci USA 98:4221–4226PubMedGoogle Scholar
  201. 201.
    Sabolic I, Dembic Z (1981) Alcohol dehydrogenase in mouse tissues: sex differences and testosterone effect. Period Biol 83:307–313Google Scholar
  202. 202.
    Sabolic I, Herak-Kramberger CM, Ljubojevic M, Kusan M, Matokanovic M, Balen D, Kusec V, Brown D (2005) Gender differences exist in the expression of AQP1 along the rat nephron. The 4th Int. Conference on Aquaporins, Genval (Brussels), Belgium, Abstract Book, p. 83Google Scholar
  203. 203.
    Sabolic I, Skarica M, Gorboulev V, Ljubojevic M, Balen D, Herak-Kramberger CM, Koepsell H (2006) Rat renal glucose transporter SGLT1 exhibits zonal distribution and androgen-dependent gender differences. Am J Physiol Renal Physiol 290:F913–F926PubMedGoogle Scholar
  204. 204.
    Saito H, Masuda S, Inui K (1996) Cloning and functional characterization of a novel rat organic anion transporter mediating basolateral uptake of methotrexate in the kidney. J Biol Chem 271:20719–20725PubMedGoogle Scholar
  205. 205.
    Sakemi T, Ohtsuka N, Tomiyaoshi Y, Morito F (1996) Sex difference in progression of adriamycin-induced nephropathy in rats. Am J Nephrol 16:540–547PubMedGoogle Scholar
  206. 206.
    Sakurai Y, Motohashi H, Ueo H, Masuda S, Saito H, Okuda M, Mori N, Matsuura M, Doi T, Fukatsu A, Ogawa O, Inui K (2004) Expression levels of renal organic anion transporters (OATs) and their correlation with anionic drug excretion in patients with renal diseases. Pharm Res 21:61–67PubMedGoogle Scholar
  207. 207.
    Sanchez-Capelo A, Tejada F, Ruzafa C, Cremades A, Penafiel R (1999) Postnatal exposure to androgens alters renal ornithine decarboxylase ontogeny and abolishes renal sexual dimorphism in mice. Biol Neonat 76:72–83Google Scholar
  208. 208.
    Sandhu S, Silbiger SR, Lei J, Neugarten J (1997) Effects of sex hormones on fluid and solute transport in Madin-Darby canine kidney cells. Kidney Int 51:1535–1539PubMedGoogle Scholar
  209. 209.
    Sato M, Suzaki H, Miyazaki H (2000) Sex-related differences in urinary excretion of egualen sodium in rats. Drug Metab Dispos 28:21–27PubMedGoogle Scholar
  210. 210.
    Satoh J, Romero MF (2002) Mg2+ transport in the kidney. BioMetals 15:285–295PubMedGoogle Scholar
  211. 211.
    Sardeli C, Li C, Known TH, Knepper MA, Nielsen S, Frokiaer J (2000) Aquaporin-2 expression is increased in rat kidneys after ovariectomy. FASEB J 14:A345 (Abstract)Google Scholar
  212. 212.
    Scheffer GL, Haas M, Vree JM, Pijnenborg AC, Bosman DK, Elferink RP, Valk P, Borst P, Scheper RJ (2002) Tissue distribution and induction of human multidrug resistant protein 3. Lab Invest 82:193–201PubMedGoogle Scholar
  213. 213.
    Scheel O, Zdebik AA, Lourdel S, Jentsch TJ (2005) Voltage-dependent electrogenic chloride/proton exchange by endosomal CLC proteins. Nature 436:421–427Google Scholar
  214. 214.
    Schiebler TH, Danner KG (1978) The effect of sex hormones on the proximal tubule in the rat kidney. Cell Tissue Res 192:527–549PubMedGoogle Scholar
  215. 215.
    Schlattjan JH, Biggemann F, Greven J (2005) Gender differences in renal tubular taurocholate transport. Naunyn-Schmiedeberg’s Arch Pharmacol 371:449–456Google Scholar
  216. 216.
    Schmidt F, Yoshimura Y, Ni RX, Kneesel S, Constantinou CE (2001) Influence of gender on diurnal variation of urine production and micturition characteristics of the rat. Neurourol Urodyn 20:287–295PubMedGoogle Scholar
  217. 217.
    Sekine T, Cha SH, Endou H (2000) The multispecific organic anion transporter (OAT) family. Pfluegers Arch Eur J Physiol 440:337–350Google Scholar
  218. 218.
    Sekine T, Miyazaki H, Endou H (2006) Molecular physiology or renal organic anion transporters. Am J Physiol Renal Physiol 290:F251–F261PubMedGoogle Scholar
  219. 219.
    Selye H (1939) The effect of testosterone on the kidney. J Urol 42:637–641Google Scholar
  220. 220.
    Shaikh ZA, Jordan SA, Tewari PC (1993) Cadmium deposition and metallothionein induction in mice - strain-dependent, sex-dependent, age-dependent and dose-dependent differences. Toxicology 80:51–70PubMedGoogle Scholar
  221. 221.
    Share L, Crofton JT, Ouchi Y (1988) Vasopressin: sexual dimorphism in secretion, cardiovascular actions and hypertension. Am J Med Sci 295:314–319PubMedGoogle Scholar
  222. 222.
    Sharma PK, Thakur MK (2004) Estrogen receptor alpha expression in mice kidney shows sex differences during aging. Biogerontology 5:375–381PubMedGoogle Scholar
  223. 223.
    Sharpe RM (1998) The roles of oestrogen in the male. Trends Endocrinol Metab 9:371–377PubMedGoogle Scholar
  224. 224.
    Shen H, Smith DE, Yang T, Huang YG, Schnermann JB, Brosius FC (1999) Localization of PEPT1 and PEPT2 proton-coupled oligopeptide transporter mRNA and protein in rat kidney. Am J Physiol Renal Physiol 276:F658–F665Google Scholar
  225. 225.
    Silbiger S, Neugarten J (1995) The impact of gender on the progression of chronic renal disease. Am J Kidney Dis 25:515–533PubMedGoogle Scholar
  226. 226.
    Singer MA (2001) Of mice and men and elephants: metabolic rate sets glomerular filtration rate. Am J Kidney Dis 37:164–178PubMedCrossRefGoogle Scholar
  227. 227.
    Slitt AL, Cherrington NJ, Hartley DP, Leazer TM, Klaassen CD (2002) Tissue distribution and renal developmental changes in rat organic cation transporter mRNA levels. Drug Metab Dispos 30:212–219PubMedGoogle Scholar
  228. 228.
    Smeets PHE, Van Aubel RAMH, Wouterse AC, Van den Heuvel JJMW, Russel FGM (2004) Contribution of multidrug resistance protein 2 (MRP2/ABCC2) to the renal excretion of p-aminohippurate (PAH) and identification of MRP4 (ABCC4) as a novel PAH transporter. J Am Soc Nephrol 15:2828–2835PubMedGoogle Scholar
  229. 229.
    Smith AG, Francis JE (1983) Evidence for the active renal secretion of S-pentachlorophenyl-N-acetyl-L-cysteine by female rats. Biochem Pharmacol 32:3797–3801PubMedGoogle Scholar
  230. 230.
    Smolen TN, Brewer JA, Weber WW (1993) Testosterone modulation of N-acetylation in mouse kidney. J Pharmacol Exp Ther 264:854–858PubMedGoogle Scholar
  231. 231.
    Snyder SH, Axelrod J (1965) Sex difference and hormonal control of histamine methyltransferase activity. Biochim Biophys Acta 111:416–421PubMedGoogle Scholar
  232. 232.
    Stamatelou KK, Francis ME, Jones CA, Nyberg LM, Curhan GC (2003) Time trends in reported prevalence of kidney stones in the United States: 1976–1994. Kidney Int 63:1817–23PubMedGoogle Scholar
  233. 233.
    Stanley EG, Bailey NJC, Bollard ME, Haselden JN, Waterfield CJ, Holmes E, Nicholson JK (2005) Sexual dimorphism in urinary metabolite profiles of Han Wistar rats revealed by nuclear-magnetic-resonance-based metabonomics. Anal Biochem 343:195–202PubMedGoogle Scholar
  234. 234.
    Stieger B, Higgins CF (guest Editors) (2007) Twenty years of ABC transporters. Pflügers Arch Eur J Physiol 453:5Google Scholar
  235. 235.
    Stock JL, Coderre JA, Burke EM, Danner DB, Chipman SD, Shapiro JR (1992) Identification of estrogen receptor mRNA and the estrogen modulation of parathyroid hormone-stimulated cyclic AMP accumulation in opossum kidney cells. J Cell Physiol 150:517–525PubMedGoogle Scholar
  236. 236.
    Stumpf WE, Sar M, Narbaitz R, Reid FA, DeLuca HF, Tanaka Y (1980) Cellular and subcellular localization of 1,25-(OH)2-vitamin D3 in rat kidney: comparison with localization of parathyroid hormone and estradiol. Proc Natl Acad Sci USA 77:1149–1153PubMedGoogle Scholar
  237. 237.
    Sturrock RD (2000) Gout, easy to misdiagnose. Brit Med J 320:132–133PubMedGoogle Scholar
  238. 238.
    Sun H, Frassetto L, Benet LZ (2006) Effects of renal failure on drug transport and metabolism. Pharmacol Ther 109:1–11PubMedGoogle Scholar
  239. 239.
    Sun JH, Langer WJ, Devish K, Lane PH (2006) Compensatory kidney growth in estrogen receptor-α null mice. Am J Physiol Renal Physiol 290:F319–F323PubMedGoogle Scholar
  240. 240.
    Suzuki S, Yoshida J, Takahashi T (1996) Effect of testosterone on carbonic anhydrase and Mg2+-dependent \({\text{HCO}}^{{\text{ - }}}_{{\text{3}}} \) stimulated ATPase activities in rat kidney-comparison with estradiol effect. Comp Biochem Physiol C Comp Pharmacol Toxicol 114:105–112Google Scholar
  241. 241.
    Sweet DH (2005) Organic anion transporter (Slc22a) family members as mediators of toxicity. Toxicol Appl Pharmacol 204:198–215PubMedGoogle Scholar
  242. 242.
    Sweet DH, Bush KT, Nigam SK (2001) The organic anion transporter family: from physiology to ontogeny and the clinic. Am J Physiol Renal Physiol 281:F197–F205PubMedGoogle Scholar
  243. 243.
    Sweet DH, Miller DS, Pritchard JB, Fujiwara Y, Beier DR, Nigam SK (2002) Impaired organic anion transport in kidney and choroid plexus of organic anion transporter 3 (Oat3 (Slc22a8)) knockout mice. J Biol Chem 277:26934–26943PubMedGoogle Scholar
  244. 244.
    Taft DR, Dontabhaktuni A, Babayeva M, Nakatani-Freshwater T, Savant IA (2006) Application of the isolated perfused rat kidney model to assess gender effects on drug excretion. Drug Dev Ind Pharm 32:919–928PubMedGoogle Scholar
  245. 245.
    Takaoka M, Yuba M, Fujii T, Ohkita M, Matsumura Y (2002) Oestrogen protects against ischaemic acute renal failure in rats by suppressing renal endothelin-I overproduction. Clin Sci 103:434S–437SPubMedGoogle Scholar
  246. 246.
    Takeda H, Chodak G, Mutchnik S, Nakamoto T, Chang C (1990) Immunohistochemical localization of androgen receptors with mono- and polyclonal antibodies to androgen receptor. J Endocrinol 126:17–25PubMedGoogle Scholar
  247. 247.
    Takeda M, Tojo A, Sekine T, Hosoyamada R, Kanai Y, Endou H (1999) Role of organic anion transporter 1 (OAT1) in cephaloridine (CER)-induced nephrotoxicity. Kidney Int 56:2128–2136PubMedGoogle Scholar
  248. 248.
    Tamai I, China K, Sai Y, Kobayashi D, Nezu J-I, Kawahara E, Tsuji A (2001) Na+-coupled transport of L-carnitine via high-affinity carnitine transporter OCTN2 and its subcellular localization in kidney. Biochim Biophys Acta 1512:273–284PubMedGoogle Scholar
  249. 249.
    Tanaka Y, Deguchi Y, Ishii I, Terai T (1991) Sex differences in excretion of zenarestat in rat. Xenobiotica 21:1119–1125PubMedGoogle Scholar
  250. 250.
    Tanaka Y, Fujiwara T, Esumi Y (1992) Sex difference in the excretion of zenarestat in mice, rats, dogs and humans. Xenobiotica 22:941–947PubMedGoogle Scholar
  251. 251.
    Tanaka Y, Kadoh Y, Mukumoto S, Ishikawa H (1991) The role of age and sex hormones on the urinary excretion of zenarestat in rats. Xenobiotica 21:1273–1279PubMedCrossRefGoogle Scholar
  252. 252.
    Tanaka Y, Slitt AL, Leazer TM, Maher JM, Klaassen CD (2005) Tissue distribution and hormonal regulation of the breast cancer resistance protein (Bcrp/Abcg2) in rats and mice. Biochem Biophys Res Commun 326:181–187PubMedGoogle Scholar
  253. 253.
    Tarloff JB, Khairallah EA, Cohen SD, Goldstein RS (1996) Sex- and age-dependent acetaminophen hepato- and nephrotoxicity in Sprague–Dawley rats—role of tissue accumulation, nonprotein sulfhydryl depletion, and covalent binding. Fund Appl Toxicol 30:13–22Google Scholar
  254. 254.
    Tarry-Adkins JL, Ozanne SE, Norden A, Cherif H, Hales CN (2006) Lower antioxidant capacity and elevated p53 and p21 may be link between gender disparity in renal telomere shortening, albuminuria, and longevity. Am J Physiol Renal Physiol 290:F509–F516PubMedGoogle Scholar
  255. 255.
    Taylor AH, Al-Azzawi F (2000) Immunolocalisation of oestrogen receptor beta in human tissues. J Mol Endocrinol 24:145–155PubMedGoogle Scholar
  256. 256.
    Terashita S, Sawamoto T, Deguchi S, Tokuma Y, Hata T (1995) Sex-dependent and independent renal excretion of nilvadipine metabolites in rat: evidence for a sex-dependent active secretion in kidney. Xenobiotica 25:37–47PubMedGoogle Scholar
  257. 257.
    Terlouw SA, Masereeuw R, Russel FGM (2003) Modulatory effects of hormones, drugs, and toxic events on renal organic anion transport. Biochem Pharmacol 65:1393–1405PubMedGoogle Scholar
  258. 258.
    Thorens B, Lodish HF, Brown D (1990) Differential localization of two glucose transporter isoforms in rat kidney. Am J Physiol Cell Physiol 259:C286–C294Google Scholar
  259. 259.
    Tran C, Knowles SR, Liu BA, Shear NH (1998) Gender differences in adverse drug reactions. J Clin Pharmacol 38:1003–1009PubMedGoogle Scholar
  260. 260.
    Trevisan A, Cristofori P, Beggio M, Venturini MB, DiMarco L, Zanetti E (2005) Segmentary effects on the renal proximal tubule due to hexachloro-1,3-butadiene in rats: biomarkers related to gender. J Appl Toxicol 25:13–19PubMedGoogle Scholar
  261. 261.
    Tsuda M, Terada T, Irie M, Katsura T, Niida A, Tomita K, Fujii N, Inui K (2006) Transport characteristics of a novel peptide transporter 1 substrate, antihypertensive drug midodrine, and its amino acid derivatives. J Pharmacol Exp Ther 318:455–460PubMedGoogle Scholar
  262. 262.
    Tucker WE, Janssen FW, Agersborg HPK, Young EM, Ruelius HW (1974) Sex- and species-related nephropathy of 6-(1-aminocyclohexanecarboxamido) penicillanic acid (cyclacillin) and its relationship to the metabolic disposition of the drug. Toxicol Appl Pharmacol 29:1–18PubMedGoogle Scholar
  263. 263.
    Uotinen N, Puustinen R, Pasanen S, Manninen T, Kivineva M, Syvala H, Tuohimaa P, Ylikomi T (1999) Distribution of progesterone receptor in female mouse tissues. Gen Comp Endocrinol 115:429–441PubMedGoogle Scholar
  264. 264.
    Urakami Y, Nakamura N, Takahashi K, Saito H, Hashimoto Y, Inui K (1999) Gender differences in expression of organic cation transporter OCT2 in rat kidney. FEBS Lett 461:339–342PubMedGoogle Scholar
  265. 265.
    Urakami Y, Okuda M, Saito H, Inui K (2000) Hormonal regulation of organic cation transporter OCT2 expression in rat kidney. FEBS Lett 473:173–176PubMedGoogle Scholar
  266. 266.
    Valle LD, Toffolo V, Vianello S, Belvedere P, Colombo L (2004) Expression of cytochrome P450c17 and other steroid-converting enzymes in the rat kidney throughout the life span. J Steroid Biochem Mol Biol 91:49–58PubMedGoogle Scholar
  267. 267.
    Van Aubel RAMH, Masereeuw R, Russel FG (2000) Molecular pharmacology of renal organic anion transporters. Am J Physiol Renal Physiol 279:F216–F232PubMedGoogle Scholar
  268. 268.
    Van Aubel RAMH, Smeets PHE, Peters JGP, Bindels RJM, Russel FGM (2002) The MRP4/ABCC4 gene encodes a novel apical organic anion transporter in human kidney proximal tubules: putative efflux pump for urinary cAMP and cGMP. J Am Soc Nephrol 13:595–603PubMedGoogle Scholar
  269. 269.
    Verzola D, Gandolfo MT, Salvatore F, Villaggio F, Gianiorio F, Traverso P, Deferrari G, Garibotto G (2004) Testosterone promotes apoptotic damage in human renal tubular cells. Kidney Int 65:1252–1261PubMedGoogle Scholar
  270. 270.
    Wang E, Yayama K, Takano M, Okamoto H (1994) Sexual dimorphism in urine angiotensinogen excretion in the rat. Jpn J Pharmacol 64:243–250PubMedGoogle Scholar
  271. 271.
    Wang YX, Crofton JT, Liu H, Brooks DP, Share L (1994) Effects of gonadectomy on sexually dimorphic antidiuretic action of vasopressin in conscious rats. Am J Physiol Regul Integr Comp Physiol 267:R536–R541Google Scholar
  272. 272.
    Wang YX, Crofton JT, Share L (1997) Sex differences in the cardiovascular and renal actions of vasopressin in conscious rats. Am J Physiol Regul Integr Comp Physiol 41:R370–R376Google Scholar
  273. 273.
    Wang YX, Edwards RM, Nambi P, Stack EJ, Pullen M, Share L, Crofton JT, Brooks DP (1993) Sex difference in the antidiuretic activity of vasopressin in the rat. Am J Physiol Regul Integr Comp Physiol 265:R1284–R1290Google Scholar
  274. 274.
    Weiner CP, Lizasoain I, Baylis SA, Knowles RG, Charles IG, Moncada S (1994) Induction of calcium-dependent nitric oxide synthases by sex hormones. Proc Nat Acad Sci USA 91:5212–5216PubMedGoogle Scholar
  275. 275.
    Wilson CM, McPhaul MJ (1996) A and B forms of the androgen receptor are expressed in a variety of human tissues. Mol Cell Endocrinol 120:51–57PubMedGoogle Scholar
  276. 276.
    Wittner M, Desfleurs E, Pajaud S, Moine G, Simeone S, DeRouffignac C, DiStefano A (1997) Calcium and magnesium transport in the cortical thick ascending limb of Henle’s loop: influence of age and gender. Pfluegers Arch Eur J Physiol 434:451–456Google Scholar
  277. 277.
    Wong LT, Escobar MR, Smyth DD, Sitar DS (1993) Gender-associated differences in rat renal tubular amantadine transport and absence of stereoselective transport inhibition by quinine and quinidine in distal tubules. J Pharmacol Exp Ther 267:1440–1444PubMedGoogle Scholar
  278. 278.
    Wong LT, Sitar DS, Aoki HY (1995) Chronic tobacco smoking and gender as variables affecting amantadine disposition in healthy subjects. Br J Clin Pharmacol 39:81–84PubMedGoogle Scholar
  279. 279.
    Xie YS, Sakatsume M, Nishi S, Narita I, Arakawa M, Gejyo F (2001) Expression, roles, receptors, and regulation of osteopontin in the kidney. Kidney Int 60:1645–1657PubMedGoogle Scholar
  280. 280.
    Yagisawa T, Ito F, Osaka Y, Amano H, Kobayashi C, Toma H (2001) The influence of sex hormones on renal osteopontin expression and urinary constituents in experimental urolithiasis. J Urol 166:1078–1082PubMedGoogle Scholar
  281. 281.
    Yonezawa A, Masuda S, Nishihara K, Yano I, Katsura T, Inui KI (2005) Association between tubular toxicity of cisplatin and expression of organic cation transporter rOCT2 (Slc22a2) in the rat. Biochem Pharmacol 70:1823–1831PubMedGoogle Scholar
  282. 282.
    Youngblood GL, Sweet DH (2004) Identification and functional assessment of the novel murine organic anion transporter Oat5 (Slc22a19) expressed in kidney. Am J Physiol Renal Physiol 287:F236–F244PubMedGoogle Scholar
  283. 283.
    Zhu BT, Conney AH (1998) Is 2-methoxyestradiol an endogenous estrogen metabolite that inhibits mammary carcinogenesis? Cancer Res 58:2269–2277PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Ivan Sabolić
    • 1
    Email author
  • Abdul R. Asif
    • 3
  • Wolfgang E. Budach
    • 2
  • Christoph Wanke
    • 2
  • Andrew Bahn
    • 3
  • Gerhard Burckhardt
    • 3
  1. 1.Molecular ToxicologyInstitute for Medical Research and Occupational HealthZagrebCroatia
  2. 2.WKL-136.1.81, Novartis Pharma AGBaselSwitzerland
  3. 3.Abteilung Vegetative Physiologie und PathophysiologieGeorg-August-Universität GöttingenGöttingenGermany

Personalised recommendations