Preferential reduction of Na+/K+ ATPase alpha3 by 17beta-estradiol influences contraction frequency in rat uteri.

: One beta1 and two alpha (alpha1 and alpha3) isoforms of Na+/K+-ATPase exist in rat uteri. Previous immunocytochemistry studies have suggested that the alpha3 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 alpha3 isoform in rats. After 1-, 2-, and 4- day treatments with 17beta-estradiol (E2, 5 microg/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 E2 decreased both contraction frequency and alpha3-protein expression without the change in uterine diameter, enzyme activity or other isoforms. Two days of E2 reduced contraction frequency, the enzyme activity, as well as alpha3- and beta1- protein abundance but increased alpha1-protein and uterine diameter. Four days of E2 elicited similar effects as two days of E2, but did not affect alpha1-protein abundance. In conclusion, E2 elicits differential effects on isoform expression. After 1-day treatment with 17beta-estradiol, the decrease in the expression of alpha3 and beta1 without a change in Na+/K+-ATPase activity suggests that some isoform other than beta1 exist in rat uteri. The positive correlation between the reduction of alpha3-and the decrease of contraction frequency suggests the involvement of alpha3 isoform in uterine oscillation.