Glucocorticoid Binding Capacity Research Articles

Aflatoxin inhibition of glucocorticoid binding capacity of rat liver nuclei

The effect of aflatoxin B 1 on the binding capacity of rat liver cytoplasmic glucocorticoid receptors and the nuclear binding of the activated receptor complex was investigated. No alterations in the kinetics of [ 3H]dexamethasonccytosol receptor complex formation were noted 2 h after treatment with 1 mg/kg aflatoxin B 1. However, a 33% decrease in the concentration of nuclear acceptor sites and a 24% decrease in the glucocorticoid receptor-nuclear binding equilibrium constant of dissociation was observed. This response was near maximal at 2 h and persisted for at least 36 h. Inhibition of nuclear binding capacity was directly related to aflatoxin B 1 dose, with a correlation coefficient of 0.99. Actinomycin D treatment (0.1 mg/kg) resulted in a slight reduction (16%) in the concentration of nuclear acceptor sites but had no effect on the nuclear binding dissociation constant. Administration of [ 3H]dexamethasone to aflatoxin B 1-treated rats produced a similar pattern of glucocortocoid binding distribution in vivo to that observed in vitro. No differences in [ 3H]dexamethasone-cytoplasmic receptor binding between control and aflatoxin B 1-treated rats were found, whereas nuclear [ 3H]dexamethasone binding was reduced 34% by aflatoxin B 1 treatment.

Glucocorticoid binding to receptor-like proteins in rat brain and pituitary: Ontogenetic and experimentally induced changes

Cytosol binding of [3H]corticosterone and [3H]dexamethasone was measured in various brain areas and the pituitary of perfused rats 12 h and 72 h, respectively, after adrenalectomy (ADX). A considerable regional heterogeneity was found 12 h post ADX representing differences of the normal cytosol binding capacities between various areas. When the second phase of the adrenalectomy-induced increase in binding capacity was allowed to develop (72 h post ADX), the cytosol binding of all regions increased to various extents. The highest percentage increases were found in those areas with the highest glucocorticoid binding capacity, namely the hippocampus and the septum. The ontogeny of the cytosol glucocorticoid binding macromolecules was investigated in the hippocampus, hypothalamus and pituitary using [3H]corticosterone and [3H]dexamethasone. The concentration of corticosterone binding sites is lowest in all three areas around day one and then increases by a factor of 2-3 reaching adult levels around day 32. For [3H]dexamethasone a similar pattern was observed in the hippocampus and hypothalamus. In the pituitary, however, the concentration of binding sites was slightly higher at day 1 than at any later developmental stage. Interruption of the fimbria in 3-day-old rats did not affect the development of the binding sites in the hippocampus. In an attempt to interfere with the normal glucocorticoid binding of the hippocampus as well as with the postadrenalectomy increase of the cytosol binding sites, bilateral transection of the fimbria was performed either 3 days or 80 days before ADX. In neither case did fimbria transection prevent the increase of the binding sites. The intrinsic (12 h post ADX) cytosol binding capacity of the hippocampus was also not affected by this lesion.

The effect of hormones on glucocorticoid binding capacity of rat liver cytosol

The relationship between the glucocorticoid binding capacity of rat liver cytosol and the activity of tyrosine aminotransferase has been studied in adrenalectomized male rats. Bilateral adrenalectomy of male rats caused an increase within 3 days in the level of specific dexamethasone binding of liver cytosol accompanied by a rapid decrease in tyrosine aminotransferase activity. Known inducers of tyrosine aminotransferase were administered in vivo to test their effect on dexamethasone binding capacity, in order to determine whether the induction was by an indirect mechanism involving an increase in glucocorticoid binding capacity. Insulin, adrenalin, glucagon, dibutyryl cyclic AMP and oestradiol caused a significant increase in the activity of the enzyme, with no change in the specific dexamethasone binding. Tetracosactrin, a synthetic analogue of ACTH, had no effect on either parameter. It was concluded that the induction of tyrosine aminotransferase by the compounds tested was not mediated by an increase in glucocorticoid receptor activity.