Estradiol renal receptor molecules and estradiol-dependent antinatriuresis.

Estradiol renal receptor molecules and estradiol-dependent antinatriuresis. A 35 % decrease in urinary excretion of sodium was produced when 1713-estradiol was administered to adrenalectomized male rats in doses of 40 jig/day. Such estrogendependent retention of sodium independent of mineralocorticoid secretion suggests the possibility of a direct effect of estrogens on the renal tubule. We here report the presence of renal estradiol receptor molecules in the cytosol fraction of rat kidney homogenates incubated at 4° C for 3.5 hr with 1 to 4 x 1O M 3H-estradiol-17t3. These estradiol receptor sites have an apparent Kassociation of 6.1 x 1010 liters/mole and a maximal binding capacity of 5.4 x 10—14 moles per mg of cytosol protein. A tenfold excess of non-radioactive estradiol reduced PH] estradiol binding by 67%; the same amount of estriol reduced binding by 45 %, while a series of nonestrogenic steroids had no significant effect on binding. After rat kidney slices were incubated at 37° C for 45 mm with io M 3H-estradiol prior to preparation of subcellular fractions, a considerable amount of estradiol (1.5 x 10—13 moles per mg of protein) was extracted from the purified nuclear fraction. The addition of a hundred-fold excess of nonradioactive estradiol to the incubation medium reduced the 3H-estradiol in the nuclear fraction by 76%, while a hundredfold excess of aldosterone had no effect on nuclear content of estradiol. These results compare favorably to those obtained with receptor molecules from other estrogen-responsive tissues and provide presumptive evidence for the involvement of renal estradiol receptor sites in the effect of estrogens on sodium excretion.