Maximal Binding Affinity Research Articles

Stress down-regulates corticosterone receptors in a site-specific manner in the brain.

We have examined whether corticosterone receptor number within the brain can be regulated by its own ligand and whether such autoregulation reduces receptor number after the sustained secretion of corticosterone during repeated stress. Glucocorticoid receptors were measured in cytosolic preparations from acutely adrenalectomized rats using [1,2,6,7-3H] dexamethasone; maximal binding and receptor affinity parameters were determined by Scatchard analysis. Sustained elevations of circulating corticosterone, whether by repeated stress or exogenous corticosterone administration, did not change receptor affinity for [3H]dexamethasone, but significantly reduced cytosolic corticosterone receptor number. This reduction in total receptor number could not be attributed to residual tissue contamination with endogenous corticosterone after adrenalectomy or to translocation of cytosolic receptors to cell nuclei. The receptor reductions were anatomically specific, occurring in the hippocampus and amygdala, but not in the hypothalamus or pituitary, and were limited, in that exogenous corticosterone plus stress reduced receptor number no more than did stress alone. Further, 3 weeks of daily administration of 5 mg corticosterone caused reductions similar to those seen after only 4 days of treatment. Finally, the declines in glucocorticoid receptor number were reversible; receptor concentrations returned to normal levels within 1 week after the cessation of treatment with exogenous corticosterone. Thus, this study presents evidence that glucocorticoid down-regulation may constitute a physiological phenomenon.

Investigations into the etiology of elevated serum T 3 levels in protein-malnourished rats

Thyroid function studies and the peripheral metabolism of thyroid hormone were examined in rats fed a low protein diet (9% casein) for 4–8 wk. Compared to animals fed a normal protein diet ad libitum, both the low protein rats and a pair-fed control group weighed less at the end of the study. However, serum total T 3 levels were significantly higher only in the protein deficient rats. The elevated serum T 3 was not explainable by enhanced peripheral T 4 to T 3 conversion, as there was no evidence of any change in hepatic or renal 5′-deiodinase activity when homogenates were examined for conversion of T 4 to T 3, reverse T 3 to 3,3′-diiodothyronine, or 3′,5′-diiodothyronine to 3′-monoiodothyronine. Neither was there an effect on hepatic T 3 receptor maximal binding capacity (204 ± 24 versus 168 ± 15 fmol/mg DNA control) or binding affinity (2.07 ± 0.38 versus 2.49 ± 0.24 × 10 −10 M control). In two separate experiments the dialyzable fraction of T 3 was significantly lower in the low protein group while free T 3 concentrations were unchanged or reduced. In contrast, serum total and free T 4 were either normal or reduced and dialyzable T 4 was unaffected by protein deficiency. We conclude that while serum total T 3 is elevated in rats chronically fed a low protein diet, this elevation is not due to enhanced T 4 to T 3 conversion. Rather, the increased T 3 levels can be accounted for by a striking alteration in protein binding to T 3. Moreover, the failure to demonstrate similar changes in serum total and dialyzable T 4 suggests that in the rat, protein deficiency has different effects on binding to the two major thyroid hormones. Dietary induced changes in serum thyroid hormone binding must be kept in mind in nutrition studies in the rat.