Glucocorticoid and mineralocorticoid receptor-binding characteristics in obese (ob/ob) mice

Adrenalectomy prevents development of obesity in genetically obese (ob/ob) mice. Replacement studies have shown that these mice exhibit hypersensitivity to corticosterone. This study was conducted to determine if this increased sensitivity was associated with alterations in corticoid receptor number or binding affinity. Cytosolic glucocorticoid receptor numbers were lower by 26% in liver, 23% in brain, and 26% in brown adipose tissue of 8-wk-old male ob/ob mice when compared with lean mice. Cytosolic glucocorticoid receptor numbers were similar in liver and brain of 4-wk-old lean and ob/ob mice is likely secondary to elevated plasma corticosterone concentrations in these older mice. Adrenalectomy increased cytosolic glucocorticoid receptor numbers in liver and brain of 8-wk-old ob/ob mice to values comparable to those in lean mice. Injection of dexamethasone (0.5 or 5 micrograms/g body wt) equally lowered cytosolic glucocorticoid receptor numbers in liver and brain of adrenalectomized ob/ob and lean mice. Brain mineralocorticoid receptor numbers and response to dexamethasone were similar in ob/ob and lean mice. These results suggest that the site responsible for increased sensitivity of ob/ob mice to corticosterone is postreceptor binding.