Estrogen directly down-regulates the bone-resorbing activity of mature osteoclasts through nuclear estrogen receptor alpha.

The decrease in estrogen level that follows the onset ofmenopause causes rapid bone loss, resulting in osteoporosis.However, the mechanism remains unclear, especially concerningthe regulation of bone-resorbing osteoclasts. Here we analyzedthe function of estrogen and its receptor in matureosteoclasts. We found that estrogen directly inhibitedbone-resorption by purified rabbit mature-osteoclasts.Moreover, using a RT-PCR technique, we report that nuclearestrogen receptor (ER) alpha but not ERbeta is expressed in mature osteoclasts. The antisense oligodeoxynucleotide for ERalpha inhibited the reductionin osteoclastic bone-resorbing activity caused by estrogen. We conclude that in part estrogen directly inhibits the bone-resorbing activity of mature osteoclasts through the ERalpha.