Enhanced serum glucocorticoid levels mediate the reduction of serosal mastcell numbers in diabetic rats

Rats turned diabetic by treatment with alloxan exhibit a significant reduct ion in serosal mast cell numbersin parallel with decreased insulin levels i n the plasma. Our aim was to investigate the putative involvement of endoge nous glucocorticoid hormone in this phenomenon. The findings indicated that rats treated with alloxan responded with an increase in levels of serum co rticosterone concomitantly with decreased mast cell numbers in the pleural space. We found that either surgical bilateral adrenalectomy or pretreatmen t with the steroid antagonist RU 486 (20 mg/kg, i.p.) impaired the drop in pleural mast cell counts in alloxinated rats. Administration of insulin (15 U/kg) prevented the increase in corticosterone levels and restored pleural mast cell levels in diabetic animals. In addition, treatment of naive rats with corticosterone (0.5 mg/kg, s.c.) or dexamethasone (0.1 mg/kg, s.c.),f or 3 consecutive days, led to a reduction in the number of mast cells recov ered from the pleural cavity as noted in diabetic animals. In contrast, ins ulin reduced serum corticosterone levels and induced a significant elevatio n in pleural mast cell numbers in naive rats. We conclude that there is a c ausative relationship between increased levels of glucocorticoids and down- regulation of mast cell numbers associated with the diabetic state, both ph enomena clearly sensitive to insulin. (C) 2001 Elsevier Science Inc. All ri ghts reserved.