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 Madin-Darby canine kidney (MDCK) cells grown on collagen-coated cell culture inserts to control media, or to estradiol or testosterone (1 nM-1 microM). Compared to control and estradiol-treated cells, testosterone stimulated fluid secretion in a dose-dependent manner, enhancing fluid secretion 4.8-fold at 1 nM and 19.7-fold at 1 microM (0.59 +/- 0.18 vs. 0.03 +/- 0.01 microliter/cm2/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 microM (81.3 +/- 30.7 vs. 6.6 +/- 3.3 pmol/mg protein, P < 0.001). GDP beta S (500 microM), an inhibitor of Gs, and 2',3'-dideoxyadenosine (10 microM), an inhibitor of the catalytic subunit of adenylate cyclase, suppressed testosterone-induced fluid and solute secretion. Neither testosterone nor estradiol had any effect on microsomal Na,K-ATPase activity, cellular proliferation or cellular total protein content. Our studies show that testosterone stimulates fluid secretion and solute transport by MDCK cells by increasing cAMP generation. In vivo, testosterone may contribute to cyst expansion by enhancing fluid secretion. This observation may help explain the worse prognosis of polycystic kidney disease observed in men.
Sandhu
S
S
Department of Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, USA.
Silbiger
S R
SR
Lei
J
J
Neugarten
J
J
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D004285:Dogs; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D016891:Polycystic Kidney, Autosomal Dominant / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology; D013739:Testosterone / Q000494:pharmacology
D012739:Gonadal Steroid Hormones; D005576:Colforsin; D013739:Testosterone; D000242:Cyclic AMP; D000254:Sodium-Potassium-Exchanging ATPase