Increased type II glucocorticoid-receptor numbers and glucocorticoid-sensitive enzyme activities in the brain of the obese Zucker rat.

The possibility that the glucocorticoid-dependence of obesity of the obese fa/fa rat reflects on overactivity of glucocorticoids on the brain has been investigated by studies of enzyme activities and glucocorticoid type II (GR) receptors. The activity of 2 glucocorticoid-sensitive enzymes, glycerol-3-phosphate dehydrogenase and glutamine synthetase, were increased in the hippocampus of obese rats. In contrast malate dehydrogenase and pyruvate kinase, glucocorticoid-insensitive enzymes, were normal. Adrenalectomy of obese rats reduced glycerol-3-phosphate dehydrogenase activity to the level of lean rats. Scatchard analysis of [3H]corticosterone binding showed that the number of type II (GR) receptors was increased in the hypothalamus and hippocampus of obese rats but the affinity of these receptors was reduced. The evidence supports the hypothesis of excessive central glucocorticoid activity in the obese rat.