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Abstract

OBJECTIVE: To determine the extent of glucocorticoid counter-regulatory control in the slimming action of oleoylestrone. DESIGN: Control and adrenalectomized rats were subjected to a seven-day treatment with 3.5 mmolakgad oleoylestrone in liposomes injected i.v. continuously by implanted osmotic minipumps. SUBJECTS: Sham-operated control and adrenalectomized lean Zucker rats. MEASUREMENTS: Body weight and food intake; plasma glucose, urea, insulin, leptin and corticosterone; liver glycogen. RESULTS: Treatment with oleoyl-estrone resulted in decreases in body weight and in food intake, as well as in circulating glucose, insulin and leptin. Combined adrenalectomy and oleoyl-estrone treatment resulted in a loss of almost 15% body weight in only seven days, with a severe drop in circulating glucose and insulin, almost total disappearance of plasma leptin and liver glycogen and a 3-fold rise in circulating urea. Food intake decreased sharply, which resulted in the exhaustion of energy reserves. CONCLUSION: The results presented here, strongly support the hypothesis that glucocorticoids play an important role in the modulation of oleoyl-estrone-induced imbalance of energy intake and expenditure. The large effect of oleoyl-estrone on glucose, glycogen-and protein-derived (urea levels) energy in adrenalectomized rats, provides more evidence for the assumed protective role of glucocorticoids against the oleoyl-estrone-induced net loss of energy reserves. The results also show the powerful destabilizing effects of unchecked oleoyl-estrone on energy balance. and cafeteria-obese 9 rats, the loss of fat being dosedependent. 7 In humans, both plasma leptin 10 and oleoyl-estrone 11 are correlated with their fat mass. Chronic administration of oleoyl-estrone in liposomes induces a decrease in leptin production and concentrations, as well as a transient rise in plasma glucocorticoid concentrations, 12 with only limited increases in hypothalamic CRH. 13Glucocorticoids protect the body fat stores by counter-regulating the effects of lipolytic agents. 14 High cortisol or corticosterone levels are associated with the maintenance of body fat reserves and obesity, as well as insulin resistance. 15 The increase in glucocorticoids contributes to the down-regulation of receptors when thermogenesis is stimulated by adrenergic agonists. 16 Adrenalectomy may prevent the development of some types of obesity, 17 but not all, 18 and it may affect fat accumulation of the already obese. 19The action of glucocorticoids is further modulated by corticosterone binding globulin (CBG), a protein synthesized by liver and other tissues.20 Most circulating glucocorticoid is bound to plasma CBG. 21 The expression and levels of CBG are controlled by glucocorticoids.22 Its main role is probably to compete with cell receptors for the available hormone, thus acting as a modulator of the amount of hormone that reaches the cell binding sites. 23The obese often show enhanced sensitivity to glucocorticoids, 24 and they maintain high circulating International Jour...