The challenge of continuous exogenous glucocorticoid administration in mice.
BACKGROUND
Chronic administration of exogenous glucocorticoids is often required in experimental research. We compared the efficacy and reliability of three different methods of continuous glucocorticoid administration in mice.


METHODS
Male CD1 Swiss White mice aged 7-9 weeks received corticosterone (CS) or carrier by either subcutaneous (s.c.) injection (n=15), s.c. implantation of micro-osmotic pumps (n=20) or s.c. implantation of slow-release pellets (n=20). Serial blood samples were taken for the measurement of plasma CS and osteocalcin (OC). Bone structural parameters were analysed by micro-computed tomography (micro-CT) in animals treated via slow-release pellets for 4 weeks.


RESULTS
Injection of CS (10 mg/kg) resulted in peak plasma CS levels of up to 2600 microg/L after 1 h, with levels returning to baseline within 4 h post-injection. Micro-osmotic pumps failed to consistently alter plasma CS levels and had variable effects on plasma OC levels. Implantation of 10 mg CS pellets induced hypercorticosteronemia within 24 h but levels returned to baseline within 7 days. Plasma OC levels fell rapidly on day 1 and remained suppressed until day 7. Weekly replacement of pellets maintained elevated plasma CS and suppressed plasma OC concentrations, and resulted in significant bone loss at the tibia and spine after 28 days.


CONCLUSIONS
Once-weekly s.c. implantation of slow-release pellets to mice appears to result in relatively consistent plasma CS and OC levels with significant biological effects. However, at least in our hands, no method delivered CS at a constant rate and variability in plasma CS levels was pronounced.
Herrmann
Markus
M
ANZAC Research Institute, The University of Sydney, and Department of Endocrinology and Metabolism, Concord Hospital, Hospital Road, Gate 3, Concord, NSW 2139, Australia. markusherr@aol.com
Henneicke
Holger
H
Street
Janine
J
Modzelewski
James
J
Kalak
Robert
R
Buttgereit
Frank
F
Dunstan
Colin R
CR
Zhou
Hong
H
Seibel
Markus J
MJ
D000818:Animals; D002908:Chronic Disease; D003345:Corticosterone / Q000008:administration & dosage / Q000633:toxicity; D016503:Drug Delivery Systems / Q000379:methods*; D004343:Drug Implants; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000633:toxicity; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D009995:Osmosis; D013997:Time Factors
D004343:Drug Implants; D005938:Glucocorticoids; D003345:Corticosterone