Abstract

Estradiol-17? increases the degranulation of blood eosinophils at high doses only. Considering the previously reported potent eosinophil-degranulating action of estradiol-17?, we investigated the dose-response for eosinophil degranulation in vivo and in vitro induced by this steroid. Very low doses of estradiol-17? induced a near-tomaximal eosinophil degranulatory response, suggesting a receptor-mediated process in which estrogen receptors displaying a much stronger affinity for estradiol-17? than for the ?-stereoisomer are involved. In addition, the effect of the different steroid doses on the within-individual residual variability was investigated. In contrast to the low hormone doses that are sufficient to induce a near-to-maximal response, the within-individual residual variability increased at high doses only. This may reflect a disruption of the homeostatic mechanisms, which occurs only at high doses. It is proposed that the evaluation of doses altering homeostatic mechanisms may provide a method for description of doses beyond which a response becomes pharmacological or pathological, reflecting a state of disease or at least abnormality of the individual. © 1997 Chapman & Hall.