AGE-RELATED-CHANGES IN THE INDUCTION OF TYROSINE AMINOTRANSFERASE BY DEXAMETHASONE - CORRELATION WITH THE LOW-AFFINITY GLUCOCORTICOID BINDING-SITES

Rat liver membranes contain Low-affinity glucocorticoid binding sites (LAGS), capable of binding with low affinity (K-d approximate to 100 n M) endogenous glucocorticoids. Unlike the glucocorticoid receptor (GR) , the LAGS level undergoes abrupt changes throughout life. The investi gation of these changes may be useful in determining whether the LAGS are involved in the cellular response to glucocorticoids. For this pur pose, we have studied glucocorticoid induction of tyrosine aminotransf erase (TAT), and its relationship with the LAGS level in adrenalectomi zed and fasted rats of different ages. No significant differences in t he GR level, or in its K-d and activation, were observed among rats of 1, 3, and 12 months of age. On the other hand, the LAGS level showed an important variation with age, from almost undetectable in 1-month-o ld rats, to a maximum value in 3-month-old rats. With respect to TAT a ctivity, an increase with age in the threshold of response to dexameth asone (DEX) administration was observed. The smallest dose of DEX capa ble of provoking a significant TAT induction rose from 0.1 mu g/kg bod y wt. in 1-month-old rats to 10 mu g/kg body wt. in 12-month-old rats. However, the smallest dose of DEX able to elicit the maximal response was 10 mu g/kg body wt. in all the assayed ages. This dose provoked a 40% decrease in the GR level, but did not significantly modify the LA GS content. From these results, we conclude that there is an age-relat ed change in the threshold of response to DEX that cannot be explained by the GR-glucocorticoid interaction. The possibility that the LAGS m odulate the cell response to glucocorticoids arises from the coinciden ce of this change with that observed in the LAGS concentration through out life.