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a Renal Unit and Program in Membrane Biology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114
b Unit of Molecular Toxicology, Institute for Medical Research and Occupational Health, 10001 Zagreb, Croatia
Reabsorption of fluid and solutes across the epithelium lining the male excurrent duct is important for adequate sperm maturation, concentration, and storage. Water channels contribute to water movement across epithelia in many tissues. Aquaporin 9 (AQP9) is abundantly expressed in the apical membrane of principal cells that line the epididymis, and in reabsorptive and secretory epithelial cells of the male reproductive tract. In this study we show that the nonsteroidal antiandrogen flutamide, given to adult rats at a dose of 50 mg kg-1 day-1 for 2 wk via osmotic minipumps significantly decreased the amount of AQP9 in the epididymis. This down-regulation was observed by immunofluorescence of cryostat tissue sections and by Western blotting of epididymal brush border membrane preparations. In addition, castrated adult rats showed lower levels of epididymal AQP9 compared with adult controls, whereas systemic testosterone treatment of castrated adult rats induced a recovery of the expression of AQP9 to control levels. These data indicate that the expression of AQP9, a likely candidate for apical transepithelial fluid and solute transport in several regions of the male reproductive tract, is modulated by androgens in the adult rat epididymis.
1 This work was supported by NIH grants HD40793 (S.B.), DK38452 (D.B. and S.B.), DK55864 (A.V.H.), and a Fogarty International Research Collaborative Award 1-R03-TW01057-01 (I.S. and D.B.). The Microscopy Core Facility of the MGH Program in Membrane Biology is additionally supported by a CSIBD Center grant DK43351 and a DERC award DK57521. Research fellowships from INSERM, the Fondation Arthur Sachs (as part of the Fullbright Program), L'Assistance Publique and the Association des Femmes Diplômées des Universités supported C.I.-B. N.P.-S. was supported by an NIH NRSA award HD08684.
2 Correspondence: Sylvie Breton, Program in Membrane Biology/Renal Unit, Massachusetts General Hospital East, 149 13th Street, 8th Floor, Charlestown, MA 02129. FAX: 617 726 5669;sbreton;careceptor.mgh.harvard.edu
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