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 mous e are a target for estrogen. The loss of estrogen receptor (ER) function th rough either knockout technology (alpha ERKO mouse) or chemical interferenc e (pure antagonist, ICI 182 780) results in a failure of a major function o f the ED, the reabsorption of testicular fluids. The purpose of this study was to test the hypothesis that estrogen controls fluid (water) reabsorptio n in the ED by modulating ion transporters important for passive water move ment 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 ex perimental 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 tre ated with ICI 182780 (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 IC I 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 th at appeared to be a cellular effect and not a direct estrogen effect. The l oss of ER alpha control resulted in an increase in mRNA abundance for the c atalytic subunit of Na+-K+ ATPase alpha1, whereas an increase in the mRNA a bundance of the Cl-/HCO3- exchanger and the chloride channel cystic fibrosi s transmembrane regulator was significantly ER beta mediated. Our results i ndicate for the first time that estrogen acting directly and indirectly thr ough both ER alpha and ER beta probably modulates fluid reabsorption in the adult mouse ED by regulating the expression of ion transporters involved i n the movement of Na+ and Cl-.