Corticosterone concentrations in the mouse.

The report of Monjan and Collector (1) emphasizes the modulating effects of stress on the immune response in mice. This important and timely contribution strengthens a growing awareness that either intentional or uncontrolled anxietystress in various forms can have critical effects on immunological and pathological reactions in-mice and other experimental animals. There are some technical matters in their report, however, that require clarification. The authors' use of the terms "cortisol" and "cortisone" when referring to circulating plasma glucocorticoids in the mouse may have been inadvertent, but is, of course, scientifically incorrect. Unlike the case in man, dogs, rabbits, and certain other mammals that produce both cortisol and corticosterone, recent experiments have shown that in the mouse corticosterone is the only glucocorticoid found in the plasma (2-4). Using a microfluorescence assay and a column chromatographic separation procedure, we have demonstrated that cortisol is not present in plasma obtained from either normal quiescent mice or from mice that have been stressed in various ways. Even in pregnant mice where plasma concentrations of corticosterone were increased to 3600 ng/ml, no coritsol was present (5). It is also unlikely that "cortisone" could be present to act on lymphocytes since cortisone is not secreted by the adrenal gland and is normally found only in the liver of cortisol-producing mammals as a short-lived metabolite of cortisol (6). The radioimmune assay (RIA) kit employed by Monjan and Collector was designed for the measurement of cortisol in patients and other mammals where the predominant circulating glucocorticoid is cortisol. That this RIA cortisol procedure cross-reacts with corticosterone to an extensive degree is evident from their results. However, since the extent of the cross-reaction is unknown, it is difficult to deduce the actual plasma corticosterone concentrations based on the "cortisol" values which were reported. Additional items of information needed for a better evaluation and appreciation of their important results are: (i) the time of day at which blood samples were obtained from their stressed mice and (ii) the specific procedures employed in handling the mice and in obtaining blood samples. The fluctuating concentration of plasma corticosterone in the mouse follows a circadian rhythm, ranging between 5 and 35 ng/ml in the morning and early afternoon but increasing to over 200 ng/ml between 7 and 10