AJP - Endocrinology and Metabolism, Vol 261, Issue 1 E126-E131, Copyright © 1991 by American Physiological Society
Adrenal steroid receptor activation in vivo and immune function
A. H. Miller, R. L. Spencer, R. L. Trestman, C. Kim, B. S. McEwen and M. Stein
Department of Psychiatry, Mount Sinai School of Medicine, New York 10029.
Recent studies have indicated significant differences among immune and
other tissues in in vivo adrenal steroid receptor activation after a given
hormone exposure. Nevertheless, the relationship between in vivo receptor
activation and functional measures of the immune response has not been
determined. Type I and type II adrenal steroid receptor binding in
conjunction with mitogen-induced T-cell proliferative responses were
measured in the spleens of Sprague-Dawley rats that were administered
various concentrations of dexamethasone (DEX). A linear relationship
between type II receptor binding and splenocyte proliferation was found,
with decreases in measurable type II receptors (indicating in vivo receptor
activation) being highly correlated with decreases in immune function.
There was no evidence of spare type II receptors. In vitro studies using
the type II receptor antagonist RU 486 confirmed that the inhibitory effect
of DEX on splenocyte proliferation was mediated via the type II receptor.
These findings provide a foundation for future studies evaluating
glucocorticoid effects on immune system function and suggest that evidence
of in vivo receptor activation may be critical for predicting when and in
which tissues adrenal steroid hormones may be capable of modulating the
immune response.
