SAT273 Characterizing The Diurnal Rhythm And Duration Of Adrenal Suppression Following Weeklong Corticosterone Treatment And Withdrawal

Abstract

Abstract Disclosure: C.N. Snyder: None. J.L. Spencer-Segal: None. Exogenous or endogenous glucocorticoid can create a dependence on glucocorticoid excess that manifests as a withdrawal syndrome during attempted taper. The etiology of this syndrome is unclear, and mechanistic understanding is hampered by the lack of a suitable mouse model. Here we present results from one attempt to define a suitable mouse model of chronic glucocorticoid excess and withdrawal. Male mice were treated with corticosterone (45μg/mL) in 1% ethanol in the drinking water for one week prior to withdrawal to a lower dose (10μg/mL) or complete withdrawal (vehicle). Control groups received vehicle or corticosterone 45μg/mL without withdrawal. Tail vein blood samples were collected from mice numerous times during the withdrawal and plasma levels of corticosterone were measured using an Enzyme Immunoassay (Arbor Assays) to determine circulating levels of corticosterone achieved at the diurnal peak and trough during treatment and withdrawal. There were three main goals of this study: (1) measure the circulating levels of corticosterone achieved at the peak and trough using this treatment paradigm (2) determine if 10μg/mL was a physiologic dose during the withdrawal period, and (3) to determine the duration of HPA axis suppression. Results showed that the diurnal rhythm of corticosterone in the treated mice was the opposite of control such that corticosterone levels were high in the morning and low in the evening. Corticosterone levels returned to control levels within 24 hours of withdrawal to 10μg/mL. When withdrawn completely, corticosterone levels decrease below control levels twenty-four hours into the withdrawal but begin to return to baseline by seventy-two hours post-withdrawal indicating rapid recovery of the endogenous HPA axis. This shows that providing corticosterone to mice in the drinking water alters the diurnal peak and trough of circulating corticosterone without continuous corticosterone elevation or prolonged HPA axis suppression. This disruption of the diurnal peak and trough should be considered in the interpretation of studies using chronic corticosterone in the drinking water. Further, this model may not be suitable for studying glucocorticoid withdrawal from chronic excess as the level of corticosterone drops below control at time points in this treatment model. Presentation: Saturday, June 17, 2023