Genetic studies on the mechanism of action of aldosterone in mice

Aldosterone reduced the urinary sodium:creatinine ratio and increased the potassium:creatinine ratio in a CBA strain of mice. In the Peru strain, under the same conditions, aldosterone had no detectable effect on the sodium:creatinine ratio but had an even more marked effect on the potassium:creatinine ratio. Thus, the effect of aldosterone on potassium excretion is separable from and is not simply a secondary consequence of the effect on sodium retention. Specific binding of 3H-aldosterone to kidney was reduced in Peru mice compared to CBA. However the correlation between 3H-aldosterone binding and physiological effect of the hormone on sodium excretion disappeared totally in a second generation cross between the strains. A possible explanation is that the nuclear binding of 3H-aldosterone as measured here was heterogeneous. In this same second generation cross, the ratio of bound nuclear 3H-aldosterone extracted by low-ionic strength Tris, to the residue of nuclear 3H-aldosterone resistant to extraction by 0.4M KCl, was strongly correlated to the ratio of the effect of aldosterone on potassium excretion to that on sodium excretion. Thus in these experiments the type of nuclear binding was correlated to the type of physiological effect. These results imply that the specific binding of aldosterone to renal tissue was, in some way at least, related to the mechanism of action of the hormone; and that the heterogeneity of this binding had functional significance in terms of the separable effects of aldosterone on renal sodium retention and potassium excretion in these two strains of mice.