Continuous corticosterone delivery via the drinking water or pellet implantation: A comparative study in mice.
In order to investigate the effects of glucocorticoid excess in rodent models, reliable methods of continuous glucocorticoid delivery are essential. The current study compares two methods of corticosterone (CS) delivery in regards to their ability to induce typical adverse outcomes such as fat accrual, insulin resistance, sarcopenia and bone loss. Eight-week-old mice received CS for 4weeks either via the drinking water (25-100μgCS/mL) or through weekly surgical implantation of slow release pellets containing 1.5mg CS. Both methods induced abnormal fat mass accrual, inhibited lean mass accretion and bone expansion, suppressed serum osteocalcin levels and induced severe insulin resistance. There was a clear dose dependant relationship between the CS concentrations in the drinking water and the severity of the phenotype, with a concentration of 50μg CS/mL drinking water most closely matching the metabolic changes induced by weekly pellet implantations. In contrast to pellets, however, delivery of CS via the drinking water resulted in a consistent diurnal exposure pattern, closely mimicking the kinetics of clinical glucocorticoid therapy. In addition, the method is safe, inexpensive, easily adjustable, non-invasive and avoids operative stress to the animals. Our data demonstrate that delivery of CS via the drinking water has advantages over weekly implantations of slow-release pellets. A dose of 50μg CS/mL drinking water is appropriate for the investigation of chronic glucocorticoid excess in mice.
Bone Research Program, ANZAC Research Institute, The University of Sydney, Sydney, Australia. Electronic address: sylvia.gasparini@sydney.edu.au.
Sylvia J
SJ
Gasparini
Bone Research Program, ANZAC Research Institute, The University of Sydney, Sydney, Australia; Department of Rheumatology and Clinical Immunology, Charité University Hospital, Berlin, Germany.
Marie-Christin
MC
Weber
Bone Research Program, ANZAC Research Institute, The University of Sydney, Sydney, Australia; DFG-Center for Regenerative Therapies, Technische Universität Dresden, Dresden, Germany.
Holger
H
Henneicke
Bone Research Program, ANZAC Research Institute, The University of Sydney, Sydney, Australia.
Sarah
S
Kim
Bone Research Program, ANZAC Research Institute, The University of Sydney, Sydney, Australia.
Hong
H
Zhou
Bone Research Program, ANZAC Research Institute, The University of Sydney, Sydney, Australia; Concord Medical School, The University of Sydney, Sydney, Australia. Electronic address: markus.seibel@sydney.edu.au.
Markus J
MJ
Seibel
D000818:Animals; D003345:Corticosterone / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D003480:Cushing Syndrome / Q000097:blood / Q000188:drug therapy; D060766:Drinking Water / Q000008:administration & dosage* / Q000737:chemistry*; D004343:Drug Implants / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D051379:Mice; D015675:Osteocalcin / Q000097:blood; D010024:Osteoporosis / Q000097:blood / Q000188:drug therapy; D055948:Sarcopenia / Q000097:blood / Q000188:drug therapy
D060766:Drinking Water; D004343:Drug Implants; D015675:Osteocalcin; D003345:Corticosterone
Corticosterone delivery; Glucocorticoid-induced dysmetabolism; Hypercortisolism; Insulin-resistance; Osteoporosis; Sarcopenia