LOW-DOSES OF ESTRADIOL-17-ALPHA DEGRANULATE BLOOD EOSINOPHIL LEUKOCYTES AND HIGH-DOSES ALTER HOMEOSTATIC MECHANISMS

Estradiol-17 beta increases the degranulation of blood eosinophils at high doses only. Considering the previously reported potent eosinophil -degranulating action of estradiol-17 alpha, we investigated the dose- response for eosinophil degranulation in vivo and in vitro induced by this steroid. Very low doses of estradiol-17 alpha induced a near-to-m aximal eosinophil degranulatory response, suggesting a receptor-mediat ed process in which estrogen receptors displaying a much stronger affi nity for estradiol-17 alpha than for the beta-stereoisomer are involve d. In addition, the effect of the different steroid doses on the withi n-individual residual variability was investigated. In contrast to the low hormone doses that are sufficient to induce a near-to-maximal res ponse, the within-individual residual variability increased at high do ses only. This may reflect a disruption of the homeostatic mechanisms, which occurs only at high doses. It is proposed that the evaluation o f doses altering homeostatic mechanisms may provide a method for descr iption of doses beyond which a response becomes pharmacological or pat hological, reflecting a state of disease or at least abnormality of th e individual.