Preferential reduction of Na ⁺ /K ⁺ ATPase α3 by 17β-estradiol influences contraction frequency in rat uteri

One β1 and two α (α1 and α3) isoforms of Na ⁺ /K ⁺ -ATPase exist in rat uteri. Previous immunocytochemistry studies have suggested that the α3 isoform may be involved in calcium regulation indirectly. Estrogens are known to both modulate Na ⁺ /K ⁺ -ATPase activities in non-uterine tissues and suppress spontaneous uterine contractions in rats. Thus the purpose of this study was to examine the correlation between estrogens-modulated uterine contraction and the expression of Na ⁺ /K ⁺ -ATPase α3 isoform in rats. After 1-, 2-, and 4- day treatments with 17β-estradiol (E ₂ , 5 μg/ml/kg, s.c., daily), the diameter of uterine horn was measured. The contraction force of uterine strips was measured by standard muscle bath apparatus. The protein abundance and enzyme activity of Na ⁺ /K ⁺ -ATPase in rat uteri were measured by Western blot analysis and ATPase assay, respectively. One day of E ₂ decreased both contraction frequency and α3-protein expression without the change in uterine diameter, enzyme activity or other isoforms. Two days of E ₂ reduced contraction frequency, the enzyme activity, as well as α3- and β1- protein abundance but increased α1-protein and uterine diameter. Four days of E ₂ elicited similar effects as two days of E ₂ , but did not affect α1-protein abundance. In conclusion, E ₂ elicits differential effects on isoform expression. After 1-day treatment with 17β-estradiol, the decrease in the expression of α3 and β1 without a change in Na ⁺ /K ⁺ -ATPase activity suggests that some isoform other than β1 exist in rat uteri. The positive correlation between the reduction of α3-and the decrease of contraction frequency suggests the involvement of α3 isoform in uterine oscillation.