DEVELOPMENTAL EXPOSURE TO ESTROGENS INDUCES PERSISTENT CHANGES IN SKELETAL TISSUE

Short-term exposure to estrogens during development has been reported to cause irreversible changes including neoplasia in estrogen target tissues, i.e. reproductive tract and mammary gland. Moreover, it has been established that estrogens have a dramatic effect on bone turnover. The recent demonstration of a low level of estrogen receptor (ER) in bone cells strongly suggests that these estrogenic effects are direct. This report was designed to evaluate whether neonatal exposure to diethylstilbestrol (DES) induces irreversible changes in bone tissue as demonstrated in other specific target organs. We show that short-term exposure of newborn mice (day 1-5) to DES (2-mu-g/pup/day) induces permanent changes in skeletal tissue in adulthood; femurs of DES-treated animals were significantly shorter than age-matched control mice. Furthermore, a significant increment (1.5 fold) in the amount of bone in the femurs (representative of long bone) and vertebrae (representative of short bone) was observed in DES-exposed animals. These data provide further evidence that bone tissue is a specific estrogen target tissue. Finally, we postulate that physiological exposure to estrogens in childhood might be one of the key factors in determining the final peak bone density in adulthood.