ADAPTATION TO ESTROGEN OVERDOSAGE

Abstract

The wt. of growing rats chronically treated with estrogens declined at first but growth subsequently resumed and body wt. exceeded the initial level despite continued massive dosages of estradiol or diethylstilbestrol. Adaptation is apparently possible without antihormone formation. Rats adapted to estradiol proved resistant to stilbestrol, chemically quite different. Conversely stilbestrol pretreatment developed resistance to the toxic actions of estradiol. This is interpreted as acquired resistance to a certain estrogenic pharmacological action rather than to a particular chemical substance. Prolonged daily adm. of large doses of estrogens resulted in gradual loss of aquired adaptation in which, following an initial wt. loss with subsequent resumption of wt. gain, the animals ultimately lost wt. despite continued treatment, and finally died after 2 or 3 mo. of estrogen adm. Adaptation to the toxic actions of estrogens occurs in the same manner as adaptation to most noxious agents, by development of the "general adaptation syndrome" with its characteristic 3 stages. Support is given the concept that adaptability is a limited quantity, gradually consumed when resistance is exerted against a stimulus to which the organism appears adapted.