Impaired conversion of rat uterine estradiol receptors during aging

We have examined the effects of aging on the capacity of rat uterine estradiol receptors to be transformed from 8S to 4S and 5S species. Cytosol receptors from mature (6-month-old) rats or senescent (24-month-old) rats have been exposed to various KCl concentrations, ammonium sulfate precipitation and 25 degrees C heating. Estradiol receptors of both the mature and senescent age groups exist in an 8S form on linear 5-20% sucrose gradients in the absence of KCl and are converted to a 4S molecule in the presence of 0.4 M KCl. At intermediate salt concentrations a greater portion of mature receptors was converted to the 4S species. At 0.15 M KCl 62.3% +/- 2.8 of the mature receptors are converted to 4S versus 41% +/- 1.9 of the senescent receptors, and at 0.2 M KCl 79.6% +/- 3.2 of the mature receptors are converted to the 4S versus 58.2% +/- 2.1 of the senescent. Ammonium sulfate treatment in the presence of 0.3 M KCl converted about 80% of the receptors from the 4S to the 5S form, while only about half of the old receptors are affected. When ammonium sulfate precipitates were heated to 25 degrees C all to mature receptors were converted to the 5S species, while only two thirds of the senescent receptors were sedimented at 5S under the same conditions. Inclusion of 20 mM molybdate during preparation blocks conversion of about 15% of the senescent receptors from the 8S to the 4S form but does not affect the mature preparations. Similarly, molybdate treatment does not affect the conversion of the mature estradiol receptors to the 5S form but increases the percentage of senescent receptors remaining in the 4S form from 30 to 45%. Such qualitative differences in receptor conversion may be related to age associated deterioration of estradiol stimulated uterine responsiveness.