Genetic conditioning of the response of rat bone tissue to estradiol.

The effects of the administration of pharmacological doses of estradiol were studied in two genetically different lines of inbred rats, at two stages of development, to gain a new insight into the genetic and physiological organization of the response of bone and Ca metabolism to exogenous estrogens. The comparative analysis of the effects on bone tissue revealed that the pattern of cellular activities at bone surfaces, the increased trabecular bone volume and the increased calcium accretion are separate responses. Likewise, the closure of the epiphyseal plate may not be associated with the curtailment of body weight increase. In addition, only one of the lines increased its intestinal calcium absorption. It appears evident that the response to exogenous estradiol relies upon the action of more than one locus. The simultaneous occurrence of partial responses (successful treatment) depends upon as yet undefined genetic and environmental (endocrine, nutritional, etc.) conditions. Extension of these conclusions to the human being implicates the recognition that a fraction of the patients undergoing estrogenic treatment may be insensitive to therapy.