Date of Award
Honors Thesis Number
Dexamethasone is a synthetic glucocorticoid which can be used to suppress the levels of glucocorticoids in the body. Thus the dexamethasone suppression test is used to evaluate the function of the negative feedback control of the hypothalamic-pituitary-adrenal axis (HPA axis). While a protocol for dexamethasone suppression testing in rats and humans has been established, an acceptable program for administration of dexamethasone to mice was lacking. In this study, mice transgenic for growth hormone, which are hypothesized to exhibit abnormal HPA control, and their normal littermates were used in three different trials in an attempt to examine the effects of dexamethasone on adrenal corticosterone secretion in mice. The first trial involved PEPCK;-hGH transgenic mice and their normal siblings. First, an orbital sinus puncture under ether anesthesia was taken at 0700 hrs in order to obtain a basal level of corticosterone. A subcutaneous injection of 0.2 ug dexamethasone 21-phosphate (DEX) /1OOg body weight was administered at 0800 hrs, and another orbital sinus puncture was taken 4 hours later. The second trial followed similar procedure but used MT-hGH transgenic mice and their normal siblings. It was concluded that the dosage of dexamethasone was insufficient in these trials since levels of corticosterone were higher at four hours post injection than at the basal time. Therefore a tenfold increased dosage (2.0 ug DEX/lOOg body weight) was used for the third trial. Normal siblings of transgenic mice were randomly assigned to either a dexamethasone or saline injection group. In addition to basal levels, corticosterone levels were measured at two and four hours post injection. The results of this experiment showed that plasma corticosterone levels in mice treated with dexamethasone were lower than in the saline control group. However, levels at post times for both groups were still elevated in comparison to basal levels. At four hours post, the dexamethasone group showed levels near the basal while the saline group was still significantly elevated. Therefore, administering 2.0ug dex/1OOg body weight significantly suppresses levels of corticosterone in mice. The issue still remains, however, why levels increased at two and four hours post injection. Further study is necessary to determine if this rise is a response due to the stress of ether, orbital sinus puncture, and handling or if it is perhaps a natural rise preceding the peak of corticosterone levels in the early evening.