Estrogen regulation of ion transporter messenger RNA levels in mouse efferent ductules are mediated differentially through estrogen receptor (ER) alpha and ER beta.
Earlier studies have shown that the efferent ductules (ED) of the male mouse are a target for estrogen. The loss of estrogen receptor (ER) function through either knockout technology (alpha ERKO mouse) or chemical interference (pure antagonist, ICI 182 780) results in a failure of a major function of the ED, the reabsorption of testicular fluids. The purpose of this study was to test the hypothesis that estrogen controls fluid (water) reabsorption in the ED by modulating ion transporters important for passive water movement through a leaky epithelium such as the ED. Northern blot analysis was used to detect the mRNA levels for key ion transporters in the following experimental groups: 1) wild-type (WT) control for the 14-day experiment, 2) ER alpha knockout (alpha ERKO) control for the 14-day experiment, 3) WT treated with ICI 182 780 (ICI) for 14 days, 4) alpha ERKO treated with ICI for 14 days, 5) WT control for the 35-day experiment, and 6) WT treated with ICI for 35 days. Estrogen differentially modulated the mRNA levels of key ion transporters. ER alpha mediated carbonic anhydrase II mRNA abundance, and there was a decrease in Na(+)/H(+) exchanger 3 mRNA levels in the alpha ERKO that appeared to be a cellular effect and not a direct estrogen effect. The loss of ER alpha control resulted in an increase in mRNA abundance for the catalytic subunit of Na(+)-K(+) ATPase alpha 1, whereas an increase in the mRNA abundance of the Cl(-)/HCO(3)(-) exchanger and the chloride channel cystic fibrosis transmembrane regulator was significantly ER beta mediated. Our results indicate for the first time that estrogen acting directly and indirectly through both ER alpha and ER beta probably modulates fluid reabsorption in the adult mouse ED by regulating the expression of ion transporters involved in the movement of Na(+) and Cl(-).
Lee
K H
KH
Departments of Animal Science and. Veterinary Biosciences, University of Illinois at Urbana-Champaign, Urbana, Illinois 61802.
Finnigan-Bunick
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C
Bahr
J
J
Bunick
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D
D000818:Animals; D017920:Antiporters; D015152:Blotting, Northern; D024402:Carbonic Anhydrase II / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens / Q000502:physiology*; D000077267:Fulvestrant; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D026901:Membrane Transport Proteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000032:analysis*; D011960:Receptors, Estrogen / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics; D000076988:Sulfate Transporters
D017920:Antiporters; D002352:Carrier Proteins; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; D011960:Receptors, Estrogen; C489860:Slc26a3 protein, mouse; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D000076988:Sulfate Transporters; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000077267:Fulvestrant; D004958:Estradiol; D024402:Carbonic Anhydrase II; D000254:Sodium-Potassium-Exchanging ATPase