Effect of cortisol on the plasma and lymphoid tissue distributions of tritiated glucocorticoids in C57BL/6 mice.
The mechanism of action of very high doses of corticosteroids, such as those administered as bolus doses in the treatment of inflammatory and immune diseases or those currently used in rodents to isolate the small proportion of medullary thymocytes considered to be corticoresistant, is still undefined. The possible existence of selective local concentration by some tissues, particularly lymphoid organs, cannot be excluded. Therefore, using C57BL/6 mice, the kinetics of lymphoid tissue and plasma radioactivities after i.p. injection of steroids, either alone or with an excess of non-radioactive cortisol hemisuccinate (up to 10 mg/animal, i.e. 500 mg/kg) were studied. There was a rapid and dose-dependent retention of [3H]corticosterone and [3H]cortisol in the thymuses of cortisol-treated compared with control animals. The spleen also appeared to be capable of accumulating steroids. However, when the tissue/plasma ratio of [3H]steroid concentration and the change in extracellular space in the presence of an excess of nonradioactive cortisol were taken into consideration, only the thymus was able to concentrate steroids above concentrations in the plasma. Moreover, this effect did not appear to be specific for glucocorticoids, since tracer accumulation was also observed when sex steroids were used as tracers. The cells of the reticulo-endothelial system may, in part, be responsible for this phenomenon of steroid concentration in lymphoid organs.
Durant
S
S
INSERM U 7, Hôpital Necker, Paris, France.
Duval
D
D
Homo-Delarche
F
F
D000818:Animals; D005260:Female; D005938:Glucocorticoids / Q000097:blood / Q000493:pharmacokinetics*; D006854:Hydrocortisone / Q000031:analogs & derivatives* / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008221:Lymphoid Tissue / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D014316:Tritium
D005938:Glucocorticoids; D014316:Tritium; C007133:hydrocortisone hemisuccinate; D006854:Hydrocortisone