ALTERATIONS IN ESTROGEN-LEVELS DURING DEVELOPMENT AFFECTS THE SKELETON - USE OF AN ANIMAL-MODEL

Exposure to estrogens during various stages of development has been sh own to irreversibly influence responsive target organs. The recent fin ding of the presence of estrogen receptor in both osteoblasts and oste oclasts has suggested a direct role of steroid hormones on bone tissue . Furthermore, estrogens have important effects on bone turnover in bo th humans and experimental animal models. Thus, this tissue is now reg arded as a specific estrogen target tissue. To investigate whether a s hort-term developmental exposure to estrogens can influence bone tissu e, we have injected female mice with diethylstilbestrol (DES) from day 1 through day 5 of life. Additionally a group of pregnant female mice were injected with different doses of DES from day 9 through 16 of pr egnancy. Mice were then weaned at 21 days of age, and effects on bone tissue of the female mice were evaluated in adulthood (7-12 months of age). These short-term treatments did not affect body weight of expose d mice. However, a dose-dependent increase in bone mass, both in the t rabecular and compact compartments, was observed in the DES-exposed fe male offspring. Furthermore, femurs from DES-exposed females were shor ter than femurs from controls. A normal skeletal mineralization accomp anied these changes in the bone tissue. in fact, a parallel increase i n total calcium content of the skeleton was found in concomitance with the increase in bone mass. Estrogen treatment induced an increase in the amount of mineralized skeleton when compared to untreated controls . In summary, this report shows that alterations of estrogen levels du ring development can influence the early phases of bone tissue develop ment inducing permanent changes in the skeleton. These changes appear to be related to bone cell programming in early phases of life.