EFFECTS OF SEX-HORMONES ON FLUID AND SOLUTE TRANSPORT IN MADIN-DARBY CANINE KIDNEY-CELLS

Polycystic kidney disease progresses more rapidly in men than in women . To investigate the basis for this sexual dimorphism, we exposed Madi n-Darby canine kidney (MDCK) cells grown on collagen-coated cell cultu re inserts to control media, or to estradiol or testosterone (1 nM-1 m u M). Compared to control and estradiol-treated cells, testosterone st imulated fluid secretion in a dose-dependent manner, enhancing fluid s ecretion 4.s-fold at 1 nM and 19.7-fold at 1 mu M (0.59 +/- 0.18 vs. 0 .03 +/- 0.01 mu l/cm(2)/hr, P < 0.001). Chloride transport paralleled fluid secretion. Testosterone increased cellular cyclic AMP levels 3.2 -fold at 1 nM and 12.3-fold at 1 mu M (51.3 +/- 30.7 vs. 6.6 +/- 3.3 p mol/mg protein, P < 0.001). GDP beta S (500 mu M), an inhibitor of Gs, and 2',3'-dideoxyadenosine (10 mu M), an inhibitor of the catalytic s ubunit of adenylate cyclase, suppressed testosterone induced fluid and solute secretion. Neither testosterone nor estradiol had any effect o n microsomal Na,K-ATPase activity, cellular proliferation or cellular total protein content. Our studies show that testosterone stimulates f luid secretion and solute transport by MDCK cells by increasing cAMP g eneration. In vivo, testosterone may contribute to cyst expansion by e nhancing fluid secretion. This observation may help explain the worse prognosis of polycystic kidney disease observed in men.