The Effects of Sustained Delivery of Corticosterone on the Adrenal Gland of Male and Female Rats

摘要

Glucocorticoids have long been recognized to have beneficial effects in rheumatoid arthritis andasthma. Numerous clinical trials show the efficacy of short term low dose treatment to resolveinflammation. Despite the success of short term use, there is concern regarding chronic use ofglucocorticoids because of the development of exogenous Cushing’s syndrome. Chronic variable stressmodels have detailed the effects of chronic stress exposure on body weight, plasma corticosteroid levels,ACTH levels, and adrenal weights, but limited studies detail the effects of the body systems induced bycontinuous exposure to glucocorticoids similar to that seen in exogenous Cushing’s syndrome. Thepresent study uses a TCPL drug delivery system to administer corticosterone (CS) continuously in maleand female animals for 24 days and evaluates long term chronic use effects on body weight, adrenalweight, and adrenal ultrastructure. Continuous release of CS resulted in slight decreases in body weightin both male and female rats and decreases in adrenal wet weight in the female rats. Ultrastructuralchanges were seen in the adrenal histology in both female and male rats. Male rat adrenal glandsshowed atrophy of the zona glomerulosa and hypertrophy of the adrenal medulla. Female rats showeddisorganization of all zones within the adrenal gland and an increase in fat around the gland. Theinformation is important for understanding physiological differences in males and females during stress.The continuous release of CS may provide insight into the pathology of exogenous Cushing’s syndrome.