In intact animals, time of drug administration may be an important factor influencing drug response. Our general goal seeks to incorporate circadian time into the study of corticosteroid regulated gene expression. This study is designed to examine fluctuations in gene expression in skeletal muscle within the 24 hour circadian cycle in normal animals. Circadian time is relevant to designing optimal corticosteroid dosing regimens. Since levels of endogenous steroid exhibit circadian fluctuations, it is our hypothesis that the expression of genes controlled by corticosteroids either directly or indirectly will also exhibit a circadian pattern in normal animals. Keywords: time series design
Overall design
Our previous studies examined changes in gene expression in response to corticosteroid treatment in adrenalectomized animals, where endogenous glucocorticoids are absent. This study is designed to examine baseline patterns of gene expression in normal animals within a 24 hour cycle. This data will be used in conjunction with future studies involving treatment of animals with corticosteroids at defined times within the circadian cycle. Fifty-four male normal Wistar rats (250-350 g body weight) were housed in a strictly controlled stress free environment with light:dark cycles of 12 hr:12hr. Three animals were sacrificed at each of 18 selected time points within the 24 hour cycle. RNA was prepared from gastrocnemius muscles for gene arrays. Time point designations reflect time after lights on in hours.
Less...
More...