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Expression of androgen receptor and androgen regulation of NDRG2 in the rat renal collecting duct

  • Renal Function, Body Fluids
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Abstract

Androgens are known to regulate gene expression in the renal proximal tubule. Whether the distal parts of the nephron, in particular the cortical collecting duct (CCD), where sodium reabsorption is controlled tightly by aldosterone, are also targets for these hormones is unknown. Real-time PCR on rat isolated renal tubules showed that androgen receptor mRNA is not only, as expected, expressed in the proximal tubule, but also in the CCD. We examined the effects of adrenalectomy (ADX) plus castration and in-vivo administration of the active metabolite of testosterone, dihydrotestosterone (DHT), on the intrarenal expression of N-myc downstream regulated gene 2 (NDRG2), an early aldosterone-induced gene located specifically in the CCD. NDRG2 belongs to a newly identified family of differentiation-related genes; although the function of these genes remains elusive, regulation of NDRG1 by androgens has been suggested. Castration plus ADX increased NDRG2 expression (RNase protection assay) significantly in the whole kidney, and a single i.p. injection of DHT caused a significant decrease in NDRG2 expression 4 h afterwards (up to 24 h). Furthermore, real-time PCR on microdissected tubules revealed that the decrease in NDRG2 expression caused by DHT is restricted to the CCD. Thus, aldosterone and androgens have opposite effects on NDRG2 expression in the renal CCD. These results are the first demonstration of androgen-dependent gene regulation in the rat renal CCD.

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References

  1. Berger FG, Watson G (1989) Androgen-regulated gene expression. Annu Rev Physiol 51:51–65

    Article  PubMed  Google Scholar 

  2. Chang C, Saltzman A, Yeh S, Young W, Keller E, Lee HJ, Wang C, Mizokami A (1995) Androgen receptor: an overview. Crit Rev Eukaryot Gene Expr 5:97–125

    PubMed  Google Scholar 

  3. Ouar Z, Sole E, Bens M, Rafestin-Oblin ME, Meseguer A, Vandewalle A (1998) Pleiotropic effects of dihydrotestosterone in immortalized mouse proximal tubule cells. Technical note. Kidney Int 53:59–66

    Article  PubMed  Google Scholar 

  4. Meseguer A, Vandewalle A (1999) Androgenic hormone action in the kidney. Curr Top Steroid Res 2:127–135

    Google Scholar 

  5. Cebrian C, Areste C, Nicolas A, Olive P, Carceller A, Piulats J, Meseguer A (2001) Kidney androgen-regulated protein interacts with cyclophilin B and reduces cyclosporine A-mediated toxicity in proximal tubule cells. J Biol Chem 276:29410–29419

    Google Scholar 

  6. Gelmann EP (2002) Molecular biology of the androgen receptor. J Clin Oncol 20:3001–15

    Article  PubMed  Google Scholar 

  7. Farman N, Rafestin-Oblin ME (2001) Multiple aspects of mineralocorticoid selectivity. Am J Physiol 280:F181–F192

    Google Scholar 

  8. Verrey F, Pearce D, Pfeiffer R, Spindler B, Mastroberardino L, Summa V, Zecevic M (2000) Pleiotropic action of aldosterone in epithelia mediated by transcription and post-transcription mechanisms. Kidney Int 57:1277–1282

    Article  PubMed  Google Scholar 

  9. Chen SY, Bhargava A, Mastroberardino L, Meijer OC, Wang J, Buse P, Firestone GL, Verrey F, Pearce D (1999) Epithelial sodium channel regulated by aldosterone-induced protein sgk. Proc Natl Acad Sci USA 96:2514–2519

    Article  PubMed  Google Scholar 

  10. Mastroberardino L, Spindler B, Forster I, Loffing J, Assandri R, May A, Verrey F (1998) Ras pathway activates epithelial Na+ channel and decreases its surface expression in Xenopus oocytes. Mol Biol Cell 9:3417–3427

    Google Scholar 

  11. Naray-Fejes-Toth A, Canessa C, Cleaveland ES, Aldrich G, Fejes-Toth G (1999) sgk is an aldosterone-induced kinase in the renal collecting duct. Effects on epithelial Na+ channels. J Biol Chem 274:16973–16978

    Google Scholar 

  12. Robert-Nicoud M, Flahaut M, Elalouf JM, Nicod M, Salinas M, Bens M, Doucet A, Wincker P, Artiguenave F, Horisberger JD, Vandewalle A, Rossier BC, Firsov D (2001) Transcriptome of a mouse kidney cortical collecting duct cell line: effects of aldosterone and vasopressin. Proc Natl Acad Sci USA 98:2712–2716

    Article  PubMed  Google Scholar 

  13. Boulkroun S, Fay M, Zennaro MC, Escoubet B, Jaisser F, Blot-Chabaud M, Farman N, Courtois-Coutry N (2002) Characterization of rat NDRG2 (N-Myc downstream regulated gene 2), a novel early mineralocorticoid-specific induced gene. J Biol Chem 277:31506–31515

    Google Scholar 

  14. Lin TM, Chang C (1997) Cloning and characterization of TDD5, an androgen target gene that is differentially repressed by testosterone and dihydrotestosterone. Proc Natl Acad Sci U S A 94:4988–4993

    Article  PubMed  Google Scholar 

  15. Ulrix W, Swinnen JV, Heyns W, Verhoeven G (1999) The differentiation-related gene 1, Drg1, is markedly upregulated by androgens in LNCaP prostatic adenocarcinoma cells. FEBS Lett 455:23–26

    Article  PubMed  Google Scholar 

  16. Kau MM, Lo MJ, Wang SW, Tsai SC, Chen JJ, Chiao YC, Yeh JY, Lin H, Shum AY, Fang VS, Ho LT, Wang PS (1999) Inhibition of aldosterone production by testosterone in male rats. Metabolism 48:1108–1114

    Article  PubMed  Google Scholar 

  17. Quinkler M, Bumke-Vogt C, Meyer B, Bähr V, Oelkers W, Diederich S (2003) The human kidney is a progesterone-metabolizing and androgen-producing organ. J Clin Endocrinol Metab 88:2803–2809

    Article  PubMed  Google Scholar 

  18. Coutry N, Farman N, Bonvalet JP, Blot-Chabaud M (1995) Synergistic action of vasopressin and aldosterone on basolateral Na+-K+-ATPase in the cortical collecting duct. J Membr Biol 145:99–106

    Google Scholar 

  19. Escoubet B, Coureau C, Bonvalet JP, Farman N (1997) Noncoordinate regulation of epithelial Na channel and Na pump subunit mRNAs in kidney and colon by aldosterone. Am J Physiol 272:C1482–C1491

    PubMed  Google Scholar 

  20. Zhou RH, Kokame K, Tsukamoto Y, Yutani C, Kato H, Miyata T (2001) Characterization of the human NDRG gene family: a newly identified member, NDRG4, is specifically expressed in brain and heart. Genomics 73:86–97

    Article  PubMed  Google Scholar 

  21. Kurdistani SK, Arizti P, Reimer CL, Sugrue MM, Aaronson SA, Lee SW (1998) Inhibition of tumor cell growth by RTP/rit42 and its responsiveness to p53 and DNA damage. Cancer Res 58:4439–4444

    PubMed  Google Scholar 

  22. van Belzen N, Dinjens WN, Diesveld MP, Groen NA, van der Made AC, Nozawa Y, Vlietstra R, Trapman J, Bosman FT (1997) A novel gene which is up-regulated during colon epithelial cell differentiation and down-regulated in colorectal neoplasms. Lab Invest 77:85–92

    PubMed  Google Scholar 

  23. Zhao W, Tang R, Huang Y, Wang W, Zhou Z, Gu S, Dai J, Ying K, Xie Y, Mao Y (2001) Cloning and expression pattern of the human NDRG3 gene. Biochim Biophys Acta 1519:134–138

    PubMed  Google Scholar 

  24. Okuda T, Kondoh H (1999) Identification of new genes ndr2 and ndr3 which are related to Ndr1/RTP/Drg1 but show distinct tissue specificity and response to N-myc. Biochem Biophys Res Commun 266:208–215

    Article  PubMed  Google Scholar 

  25. Huang AM, Rubin GM (2000) A misexpression screen identifies genes that can modulate RAS1 pathway signaling in Drosophila melanogaster. Genetics 156:1219–1230

    PubMed  Google Scholar 

  26. Hu XL, Liu P, Lin SX, Deng YC, Liu N, Li X, Yao LB (2004) NDRG2 expression and mutation in human liver and pancreatic cancers. World J Gastroenterol 10:3518–21

    Google Scholar 

  27. Tumbar T, Guasch G, Greco V, Blanpain C, Lowry WE, Rendl M, Fuchs E (2004) Defining the epithelia stem cell niche in skin. Science 303:359–363

    Google Scholar 

  28. Davidoff M, Caffier H, Schiebler TH (1980) Steroid hormone binding receptors in the rat kidney. Histochemistry 69:39–48

    Article  PubMed  Google Scholar 

  29. 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 126:17–25

    PubMed  Google Scholar 

  30. 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 139:688–695

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by INSERM. S. Boulkroun and C. LeMoellic were recipients of PhD grants of the Ministere de la Recherche et de la Technologie. We are grateful to Dr. A. Vandewalle (INSERM U478, Paris, France) for helpful discussion and critical reading of the manuscript.

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Correspondence to Nathalie Courtois-Coutry.

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Boulkroun, S., Le Moellic, C., Blot-Chabaud, M. et al. Expression of androgen receptor and androgen regulation of NDRG2 in the rat renal collecting duct. Pflugers Arch - Eur J Physiol 451, 388–394 (2005). https://doi.org/10.1007/s00424-005-1410-x

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  • DOI: https://doi.org/10.1007/s00424-005-1410-x

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